全文获取类型
收费全文 | 2161篇 |
免费 | 129篇 |
国内免费 | 10篇 |
专业分类
化学 | 1671篇 |
晶体学 | 20篇 |
力学 | 45篇 |
数学 | 209篇 |
物理学 | 355篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 29篇 |
2021年 | 49篇 |
2020年 | 38篇 |
2019年 | 56篇 |
2018年 | 37篇 |
2017年 | 36篇 |
2016年 | 102篇 |
2015年 | 72篇 |
2014年 | 111篇 |
2013年 | 210篇 |
2012年 | 189篇 |
2011年 | 175篇 |
2010年 | 130篇 |
2009年 | 108篇 |
2008年 | 120篇 |
2007年 | 118篇 |
2006年 | 124篇 |
2005年 | 106篇 |
2004年 | 83篇 |
2003年 | 80篇 |
2002年 | 102篇 |
2001年 | 39篇 |
2000年 | 28篇 |
1999年 | 24篇 |
1998年 | 17篇 |
1997年 | 15篇 |
1996年 | 16篇 |
1995年 | 10篇 |
1994年 | 13篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 3篇 |
1989年 | 8篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有2300条查询结果,搜索用时 31 毫秒
101.
Jun Myung Kim So Hyeong Sohn Noh Soo Han Prof. Seung Min Park Prof. Joohoon Kim Prof. Jae Kyu Song 《Chemphyschem》2014,15(14):2917-2921
Direct evidence for the blue luminescence of gold nanoclusters encapsulated inside hydroxyl‐terminated polyamidoamine (PAMAM) dendrimers was provided by spectroscopic studies as well as by theoretical calculations. Steady‐state and time‐resolved spectroscopic studies showed that the luminescence of the gold nanoclusters consisted largely of two electronic transitions. Theoretical calculations indicate that the two transitions are attributed to the different sizes of the gold nanoclusters (Au8 and Au13). The luminescence of the gold nanoclusters was clearly distinguished from that of the dendrimers. 相似文献
102.
Jong Young Joung Ha Yeon Lee Jongil Park Jee-Young Lee Byung Ha Chang Kyoung Tai No Ky-Youb Nam Jae Sung Hwang 《Applied biochemistry and biotechnology》2014,172(4):1882-1897
Melanocytes are unique cells that produce specific melanin-containing intracellular organelles called melanosomes. Melanosomes are transported from the perinuclear area of melanocytes toward the plasma membrane as they become more melanized in order to increase skin pigmentation. In this vesicular trafficking of melanosomes, Rab27a, melanophilin, and myosin Va play crucial roles in linking melanosomes to actin-based motors. To identify novel compounds to inhibit binding interface between Rab27a and melanophilin, a pharmacophore model was built based on a modeled 3D structure of the protein complex that describes the essential binding residues in the intermolecular interaction. A pharmacophore model was employed to screen a chemical library database. Finally, 25 virtual hits were selected for biological evaluations. The biological activities of 11 analogues were evaluated in a second assay. Two compounds were identified as having concentration-dependent inhibitory activity. By analyzing structure–activity relationships of derivatives of BMD-20, two hydroxyl functional groups were found to be critical for blocking the intermolecular binding between Rab27a and melanophilin. 相似文献
103.
Enhanced solubility of galangin based on the complexation with methylated microbial cyclosophoraoses
Hwanhee Kim Jae Min Choi Youngjin Choi Muhammad Nazir Tahir Yung-Hun Yang Eunae Cho Seunho Jung 《Journal of inclusion phenomena and macrocyclic chemistry》2014,79(3-4):291-300
Methylated cyclosophoraoses (M-Cys) were synthesized by reaction using dimethyl sulfate with native Cys (unbranched cyclic β-1,2-d-glucans) isolated from Rhizobium leguminosarum biovar viciae VF-39. Its structure was proven using nuclear magnetic resonance (1H NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Based on the enhanced hydrophobicity by methylation of Cys, we investigated the inclusion property with the water-insoluble flavonoid, galangin, through a phase solubility study using ultraviolet–visible spectroscopy. The solubility of galangin was enhanced 5.6-fold according to the added concentrations (1 mM) of M-Cys, compared to the 1.9-fold and 3.4-fold enhancements by β-Cyclodextrin (β-CD) and heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), respectively. M-Cys was also shown to have the highest binding constant (5,534 M?1) with galangin among the tested host molecules (β-CD, DM-β-CD, Cys, and M-Cys). From this result, we can infer that the complex of galangin with M-Cys is more stable than any of the other host molecules. The continuous variation method showed that the galangin/M-Cys complex was suitable for 1:1 stoichiometry. The formation of the complex was confirmed with 1H NMR, FT-IR, differential scanning calorimetry, and scanning electron microscopy. Furthermore, the hypothetical molecular model of 1:1 galangin/M-Cys complex was suggested by molecular docking simulations. The cytotoxicity to the human cervical adenocarcinoma cell lines was enhanced by the galangin/M-Cys complex compared with free galangin. The obtained results indicate that M-Cys can be utilized as an effective complexing agent for galangin. 相似文献
104.
Sangmin Jung Prof. Hyo Jae Yoon 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(12):4913-4917
The application of aziridines as nonvulnerable mechanophores is reported. Upon exposure to a mechanical force, stereochemically pure nonactivated aziridines incorporated into the backbone of a macromolecule do not undergo cis–trans isomerization, thus suggesting retention of the ring structure under force. Nonetheless, aziridines react with a dipolarophile and seem not to obey conventional reaction pathways that involve C−C or C−N bond cleavage prior to the cycloaddition. Our work demonstrates that a nonvulnerable chemical structure can be a mechanophore. 相似文献
105.
106.
Jae Won Chang Mohammed Bhuiyan Hsiu‐Ming Tsai Hannah J. Zhang Gang Li Shaghayegh Fathi David C. McCutcheon Lara Leoni Richard Freifelder Chin‐Tu Chen Raymond E. Moellering 《Angewandte Chemie (International ed. in English)》2020,59(35):15161-15165
Herein, we report the development of an 18F‐labeled, activity‐based small‐molecule probe targeting the cancer‐associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific NCEH1 labeling in live cells and animals, while permitting facile 18F radionuclide incorporation required for PET imaging. The resulting molecule, [18F]JW199, labels active NCEH1 in live cells at nanomolar concentrations and greater than 1000‐fold selectivity relative to other serine hydrolases. [18F]JW199 displays rapid, NCEH1‐dependent accumulation in mouse tissues. Finally, we demonstrate that [18F]JW199 labels aggressive cancer tumor cells in vivo, which uncovered localized NCEH1 activity at the leading edge of triple‐negative breast cancer tumors, suggesting roles for NCEH1 in tumor aggressiveness and metastasis. 相似文献
107.
Jaeyoon Kim Jae Young Shin Yun-Ho Choi Nae Gyu Kang Sanghwa Lee 《Molecules (Basel, Switzerland)》2022,27(7)
In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/β-catenin pathway by modulating the activity of Gsk3β in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3β was increased. Furthermore, the expression of β-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/β-catenin signaling through the activation of the adenosine receptor and Gsk3β plays a critical role in transmitting the signals from the adenosine receptor to β-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade. 相似文献
108.
Laily Rahmawati Sang Hee Park Dong Seon Kim Hwa Pyoung Lee Nur Aziz Chae Young Lee Seung A Kim Seok Gu Jang Dong Sam Kim Jae Youl Cho 《Molecules (Basel, Switzerland)》2022,27(1)
Prasiola japonica possesses several biological activities. However, reports on the anti-inflammatory activities and molecular mechanisms of its different solvent fractions remain limited. In this study, we investigated the potential anti-inflammatory activities of P. japonica ethanol extract (Pj-EE) and four solvent fractions of Pj-EE made with hexane (Pj-EE-HF), chloroform (Pj-EE-CF), butanol (Pj-EE-BF), or water (Pj-EE-WF) in both in vitro (LPS-induced macrophage-like RAW264.7 cells) and in vivo (carrageenan-induced acute paw edema mouse models) experiments. The most active solvent fraction was selected for further analysis. Various in vitro and in vivo assessments, including nitric oxide (NO), cytokines, luciferase assays, real-time polymerase chain reactions, and immunoblotting analyses were performed to evaluate the underlying mechanisms. In addition, the phytochemical constituents were characterized by Liquid chromatography-tandem mass spectrometry. In in vitro studies, the highest inhibition of NO production was observed in Pj-EE-CF. Further examination revealed that Pj-EE-CF decreased the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells and suppressed subsequent AP-1-luciferase activity by inhibition of phosphorylation events in the AP-1 signaling pathway. Pj-EE-CF treatment also demonstrated the strongest reduction in thickness and volume of carrageenan-induced paw edema, while Pj-EE-BF showed the lowest activity. Furthermore, Pj-EE-CF also reduced gene expression and cytokines production in tissue lysates of carrageenan-induced paw edema. These findings support and validate the evidence that Pj-EE, and especially Pj-EE-CF, could be a good natural source for an anti-inflammatory agent that targets the AP1 pathway. 相似文献
109.
Heung Jae Lee Dong Seok Kim Min Chul Suh Sang Chul Shim 《Journal of polymer science. Part A, Polymer chemistry》1996,34(16):3255-3261
2,4-Hexadiyn-1,6-diol (HDO) was polymerized on glass and silicon plates by chemical vapor deposition without transition metal catalysis to form homogeneous thin films. Structural properties of the films were investigated by FT-IR, UV-visible, Raman, x-ray diffraction, and XPS spectroscopic analyses. The structure of CVD-polymerized HDO (CVD-PHDO) films was different from that of metathesis polymerized HDO (metathesis-PHDO), showing a polyacene-based structure but no polyene structure with acetylenic side groups. © 1996 John Wiley & Sons, Inc. 相似文献
110.
Eun Kee Cho Phong K. Quach Yunfei Zhang Jae Hun Sim Tristan H. Lambert 《Chemical science》2022,13(8):2418
The use of hydrazine-catalyzed ring-closing carbonyl–olefin metathesis (RCCOM) to synthesize polycyclic heteroaromatic (PHA) compounds is described. In particular, substrates bearing Lewis basic functionalities such as pyridine rings and amines, which strongly inhibit acid catalyzed RCCOM reactions, are shown to be compatible with this reaction. Using 5 mol% catalyst loadings, a variety of PHA structures can be synthesized from biaryl alkenyl aldehydes, which themselves are readily prepared by cross-coupling.Hydrazine catalysis enables the ring-closing carbonyl–olefin metathesis (RCCOM) to form polycyclic heteroaromatics, especially those with basic functionality.Polycyclic heteroaromatic (PHA) structures comprise the core framework of many valuable compounds with a diverse range of applications (Fig. 1A).1 For example, polycyclic azines (e.g. quinolines) are embedded in many alkaloid natural products, including diplamine2 and eupolauramine3 to name just a few. These types of structures are also of interest for their biological activity, such as with the inhibitor of the Src-SH3 protein–protein interaction shown in Fig. 1A.4 Many nitrogenous PHAs are also useful as ligands for transition metal catalysis, as exemplified by the widely used ligand 1,10-phenanthroline.5 Meanwhile, chalcogenoarenes6 such as dinaphthofuran7 and benzodithiophene8 have attracted high interest for both their medicinal properties9 and especially for their potential use as organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), and organic field-effect transistors (OFETs).10 These and numerous other examples have inspired the development of a wide variety of strategies to construct PHAs.1,11–14 Although these approaches are as varied as the structures they target, the wide range of molecular configurations within PHA chemical space and the challenges inherent in exerting control over heteroatom position and global structure make novel syntheses of these structures a topic of continuing interest.Open in a separate windowFig. 1(A) Examples of PHAs. (B) RCCOM strategy for PHA synthesis. (C) Lewis base inhibition for Lewis acid vs. hydrazine catalyzed RCCOM. (D) Hydrazine-catalyzed RCCOM for PHA synthesis.One potentially advantageous strategy for PHA synthesis is the use of ring-closing carbonyl–olefin metathesis15 (RCCOM) to forge one of the PHA rings, starting from a suitably disposed alkenyl aldehyde precursor 2 that can be easily assembled by cross-coupling (Fig. 1B). In related work, the application of RCCOM to form polycyclic aromatic hydrocarbons (PAHs) was reported by Schindler in 2017.16 In this case, 5 mol% FeCl3 catalyzed the metathesis of substrates to form phenanthrenes and related compounds in high yields at room temperature. This method was highly attractive for its efficiency, its use of an earth-abundant metal catalyst, and the production of benign acetone as the only by-product. Nevertheless, one obvious drawback to the use of Lewis acid activation is that the presence of any functionality that is significantly more Lewis basic than the carbonyl group can be expected to strongly inhibit these reactions (Fig. 1C). Such a limitation thus renders this method incompatible with a wide swath of complex molecules, especially PHAs comprised of azine rings. This logic argues for a mechanistically orthogonal RCCOM approach that allows for the synthesis of PHA products with a broader range of ring systems and functional groups.We have developed an alternative approach to catalytic carbonyl–olefin metathesis that makes use of the condensation of 1,2-dialkylhydrazines 5 with aldehydes to form hydrazonium ions 6 as the key catalyst–substrate association step.17–19 This interaction has a much broader chemoorthogonality profile than Lewis acid–base interactions and should thus be much less prone to substrate inhibition than acid-catalyzed approaches. In this Communication, we demonstrate that hydrazine-catalyzed RCCOM enables the rapid assembly of PHAs bearing basic functionality (Fig. 1D).For our optimization studies, we chose biaryl pyridine aldehyde 7 as the substrate (20 salt 11 was also productive (entry 2), albeit somewhat less so. Notably, iron(iii) chloride generated no conversion at either ambient or elevated temperatures (entries 3 and 4). Trifluoroacetic acid (TFA) was similarly ineffective (entry 5). Meanwhile, a screen of various solvents revealed that, while the transformation could occur in a range of media (entries 6–9), THF was optimal. Finally, by raising the temperature to 90 °C (entry 10) or 100 °C (entry 11), up to 96% NMR yield (85% isolated yield) of adduct 8 could be obtained in the same time period.Optimization studiesa
Open in a separate windowaConditions: substrate 8 (0.2 mmol) and 5 mol% catalyst in 0.4 mL of solvent (0.5 M) in a 5 mL sealed tube were heated to the temperature indicated for 15 h. Yields were determined by 1H NMR using CH2Br2 as an internal standard.b2 equiv. of TFA was used.c85% isolated yield.Using the optimized conditions, we explored the synthesis of various PHAs (Fig. 2). In addition to benzo[h]isoquinoline (8), products 12 and 13 with fluorine substitution at various positions could be generated in good yields. Similarly, benzoisoquinolines 14 and 15 bearing electron-donating methoxy groups and the dioxole-fused product 16 were also accessed efficiently. Furthermore, a phenolic ether product 17 with a potentially acid-labile N-Boc group was generated in modest yield. We found that an even more electron-donating dimethylamino group was also compatible with this chemistry, allowing for the production of 18 in 68% yield. On the other hand, adduct 19 bearing a strongly electron-withdrawing trifluoromethyl group was isolated in only modest yield. The naphtho-fused isoquinoline 20 could be generated as well; however, 20 mol% catalyst was required to realize a 35% yield. The thiophene-fused product 21 was furnished in much better yield, also with the higher catalyst loading. Although not a heterocyclic system, we found that the reaction to form phenanthrene (22) was well-behaved, providing that compound in 83% yield. In addition, an amino-substituted phenanthrene 23 was also formed in good yield. Other thiophene-containing PAHs such as 24–26 were produced efficiently. On the other hand, adduct 27 was generated only in low yield. Naphthofuran (28), which is known to have antitumor and oestrogenic properties,21 was synthesized in good yield. Finally, pharmaceutically important structures such as benzocarbazole2229 and naphthoimidazole2330 could be accessed in moderate yields with increased catalyst loading.Open in a separate windowFig. 2Substrate scope studies for hydrazine 1-catalyzed RCCOM synthesis of polycyclic heteroaromatics. a Conditions: substrate and catalyst 1·(TFA)2 (5 mol%) in THF (0.5 M) were heated to 100 °C in a 5 mL sealed tube for 15 h. Yields were determined on purified products. b 20 mol% catalyst.We also examined the scope of the olefin substitution pattern ( Entry Substrate Time (h) Yield (%) 1 15 96 2 48 5 3b 48 27 4 48 54 5 48 64
Entry | Catalyst | Solvent | Temp. (°C) | 8 yield (%) |
---|---|---|---|---|
1 | 10 | THF | 80 | 67 |
2 | 11 | THF | 80 | 53 |
3 | FeCl3 | DCE | rt | 0 |
4 | FeCl3 | DCE | 80 | 0 |
5 | TFA | THF | 80 | 0b |
6 | 10 | i-PrOH | 80 | 31 |
7 | 10 | CH3CN | 80 | 28 |
8 | 10 | EtOAc | 80 | 26 |
9 | 10 | Toluene | 80 | 24 |
10 | 10 | THF | 90 | 87 |
11 | 10 | THF | 100 | 96c |