全文获取类型
收费全文 | 191篇 |
免费 | 18篇 |
国内免费 | 1篇 |
专业分类
化学 | 193篇 |
力学 | 1篇 |
物理学 | 16篇 |
出版年
2023年 | 2篇 |
2022年 | 12篇 |
2021年 | 18篇 |
2020年 | 14篇 |
2019年 | 7篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 10篇 |
2015年 | 10篇 |
2014年 | 8篇 |
2013年 | 8篇 |
2012年 | 11篇 |
2011年 | 12篇 |
2010年 | 13篇 |
2009年 | 9篇 |
2008年 | 10篇 |
2007年 | 13篇 |
2006年 | 11篇 |
2005年 | 3篇 |
2004年 | 9篇 |
2003年 | 6篇 |
2002年 | 1篇 |
2001年 | 2篇 |
1999年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1982年 | 1篇 |
排序方式: 共有210条查询结果,搜索用时 15 毫秒
31.
Andreas Christoforow Julian Wilke Aylin Binici Axel Pahl Claude Ostermann Sonja Sievers Herbert Waldmann 《Angewandte Chemie (International ed. in English)》2019,58(41):14715-14723
Natural products (NPs) inspire the design and synthesis of novel biologically relevant chemical matter, for instance through biology‐oriented synthesis (BIOS). However, BIOS is limited by the partial coverage of NP‐like chemical space by the guiding NPs. The design and synthesis of “pseudo NPs” overcomes these limitations by combining NP‐inspired strategies with fragment‐based compound design through de novo combination of NP‐derived fragments to unprecedented compound classes not accessible through biosynthesis. We describe the development and biological evaluation of pyrano‐furo‐pyridone (PFP) pseudo NPs, which combine pyridone‐ and dihydropyran NP fragments in three isomeric arrangements. Cheminformatic analysis indicates that the PFPs reside in an area of NP‐like chemical space not covered by existing NPs but rather by drugs and related compounds. Phenotypic profiling in a target‐agnostic “cell painting” assay revealed that PFPs induce formation of reactive oxygen species and are structurally novel inhibitors of mitochondrial complex I. 相似文献
32.
An in vitro, rapid, and quantitative cell-based assay is needed to predict the efficacy of cancer drugs in individual patients,
because a cancer patient may have unconventional aspects of tumor development. Here we report a rapid and label-free quantitative
method for verifying apoptosis in living cancer cells cultured on a sensor chip with a newly developed high-precision surface
plasmon resonance (SPR) sensor. The time-course cell reaction was monitored as the SPR angle change rate for 5 min during
a 35-min cell culture of pancreatic cancer lines with a drug. The time-course cell reaction was significantly related to cell
viability counted after 48 h as assessed by caspase-3 activity assay of apoptosis. Furthermore, the detected SPR signal was
derived from the decrease in inner mitochondrial membrane potential. The results obtained are universally valid for various
cancer drugs mediating apoptosis through different cell-signaling pathways and even for combined use in various pancreatic
cancer cell lines. This system can be applied in a clinical setting to evaluate the personal therapeutic potential of drugs
including pharmacodynamic interactions. 相似文献
33.
Zhang S Bian Z Gu C Zhang Y He S Gu N Zhang J 《Colloids and surfaces. B, Biointerfaces》2007,55(2):143-148
Maghemite nanoparticles (MNPs) were synthesized by chemical coprecipitation and coated with meso-2,3-dimercaptosuccinic acid (HOOC-CH(SH)-CH(SH)-COOH or DMSA). The morphology and properties of the nanoparticles were characterized by TEM, XRD, Zeta Potential Analyzer and VSM. Subsequentially, the anti-human cardiac troponin I (cTnI) immunomagnetic nanoparticles (IMNPs) were prepared by grafting anti-human cTnI antibodies on the surface of DMSA-coated MNPs using the linker of EDC (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride). The conjugation amount of the antibodies and the activity of IMNPs was evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting. The results show that the physical and chemical adsorption occurred at the same time, but the former was unstable and apt to desorb, and the maximum conjugation amount of antibody was about 96 μg on the 0.1 mg MNPs by covalent bond. The stability was also investigated, and after 300 days the antibodies on the IMNPs remained the biological activity. 相似文献
34.
Nilufar Z. Mamadalieva Fadia S. Youssef Hidayat Hussain Gokhan Zengin Adriano Mollica Nawal M. Al Musayeib Mohamed L. Ashour Bernhard Westermann Ludger A. Wessjohann 《Molecules (Basel, Switzerland)》2021,26(21)
The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (−7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays. 相似文献
35.
Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease and plays a key role in several biological processes, including tissue remodeling, cell migration, and matrix degradation. The inhibitors of uPA have been shown to prevent the spread of metastasis and tumor growth, and accordingly uPA is widely recognized as a target for the treatment of cancer. In this work, we report the crystal structures of the complexes of uPA with its inhibitors: 4- (aminomethyl)-benzoic acid (AMBA) and 4-(aminomethyl-phenyl)-methanol (AMPM), both at a resolution of 2.35 А. The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that AMBA is a better inhibitor for uPA (Ki = 2.68 mM) than AMPM (Ki = 13.99 mM). The structural study shows that the binding mode of inhibitor AMBA on uPA is similar to that of AMPM on uPA, both docked into the active site S1 pocket of uPA. Structural details of these complexes are provided to explain the difference of inhibitory constants. 相似文献
36.
Mattia Spano Alessandro Maccelli Giacomo Di Matteo Cinzia Ingallina Mariangela Biava Maria Elisa Crestoni Jean-Xavier Bardaud Anna Maria Giusti Alessia Mariano Anna Scotto DAbusco Anatoly P. Sobolev Alba Lasalvia Simonetta Fornarini Luisa Mannina 《Molecules (Basel, Switzerland)》2021,26(17)
The metabolite profile of fresh Goji berries from two cultivars, namely Big Lifeberry (BL) and Sweet Lifeberry (SL), grown in the Lazio region (Central Italy) and harvested at two different periods, August and October, corresponding at the beginning and the end of the maturation, was characterized by means of nuclear magnetic resonance (NMR) and electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR MS) methodologies. Several classes of compounds such as sugars, amino acids, organic acids, fatty acids, polyphenols, and terpenes were identified and quantified in hydroalcoholic and organic Bligh-Dyer extracts. Sweet Lifeberry extracts were characterized by a higher content of sucrose with respect to the Big Lifeberry ones and high levels of amino acids (glycine, betaine, proline) were observed in SL berries harvested in October. Spectrophotometric analysis of chlorophylls and total carotenoids was also carried out, showing a decrease of carotenoids during the time. These results can be useful not only to valorize local products but also to suggest the best harvesting period to obtain a product with a chemical composition suitable for specific industrial use. Finally, preliminary studies regarding both the chemical characterization of Goji leaves generally considered a waste product, and the biological activity of Big Lifeberry berries extracts was also investigated. Goji leaves showed a chemical profile rich in healthy compounds (polyphenols, flavonoids, etc.) confirming their promising use in the supplements/nutraceutical/cosmetic field. MG63 cells treated with Big Lifeberry berries extracts showed a decrease of iNOS, COX-2, IL-6, and IL-8 expression indicating their significant biological activity. 相似文献
37.
《Analytical letters》2012,45(2):65-73
Abstract 5′nucleotidase activity was measured by a coupled optical assay in which adenosine, liberated by action of the primary enzyme, released ammonia which in turn formed L-glutamate from 2-oxoglutarate and NADH. Oxidation of the latter is monitored at 340 nm. Greater activity was obtained when triethanolamine buffer, pH 7.2, and Mn++ were substituted for tris buffer, pH 7.9, and Mg++. The concentration of substrate, 5′AMP, was altered to 1 mmole/liter and that of β-glycerophosphate to 50 mmoles/liter to achieve optimal activity of true nucleotidase and suppression of 5′AMP-hydrolysis by non-specific phosphatases. 相似文献
38.
《Analytical letters》2012,45(2-3):227-241
ZnSe quantum dots (QDs) that were capped with 11-mercaptoundecanoic acid (MUA) and conjugated to amino-modified ssDNA molecules exhibited variations in fluorescence emission intensity upon hybridization with complementary ssDNA in solution, a phenomenon that can be exploited for rapid detection of free ssDNA sequences. Conjugation of MUA-capped ZnSe QDs to amino-modified ssDNA molecules resulted in increased fluorescence emission intensity and stability at room temperature. Increasing the length of the ssDNA, that was conjugated to the QDs, resulted in increased fluorescence emission intensity up to a length of about 50 nucleotide bases, beyond which the peak emission intensity reached a plateau. Hybridization of QD-ssDNA conjugates with complementary ssDNA, either in free form or bound to QDs from the same population, resulted in additional fluorescence emission intensity amplification. A small red shift was observed when three-dimensional QD-dsDNA-QD structures were formed. The QD-ssDNA sensors with single ssDNA molecule per QD were developed and used for rapid quantitative detection of fully or partially complementary free ssDNA sequences in aqueous solution. Partial hybridization of the QD-ssDNA sensors with short ssDNA targets resulted in smaller QD emission intensity amplification, when compared to full hybridization. A QD-ssDNA sensor containing a sequence corresponding to the hemoglobin beta gene was used to detect and discriminate between free ssDNA targets consisting of a complementary ssDNA sequence and targets containing a single-base mutation that can cause sickle-cell anemia. Such QD-based biosensors can form the basis for rapid separation-free assays that can be used to detect target biomolecules in solution. 相似文献
39.
Fedora Grande Maria Antonietta Occhiuzzi Maria Rosaria Perri Giuseppina Ioele Bruno Rizzuti Giancarlo Statti Antonio Garofalo 《Molecules (Basel, Switzerland)》2021,26(18)
Tacle® is a citrus fruit obtained from the crossbreeding of Clementine and Tarocco cultivars. This fruit retains a promising nutraceutical potential most likely due to a high content in polyphenols, among which the main constituents are the two glycosides naringin and hesperidin. Herein, we evaluated, through an in vitro assay, the capability of Tacle extracts to inhibit the hydroxymethylglutaryl-CoA reductase enzyme, which plays a key role in cholesterol biosynthesis. The results obtained spurred us to investigate whether the anti-enzymatic activity observed may be due to a direct interaction of aglycones naringenin and hesperetin with the enzyme catalytic site. Molecular docking simulations indicated that these two compounds are able to anchor to the protein with binding modes and affinities similar to those found for statins, which represent mainstream medications against hypercholesterolemia. The overall results showed an interesting nutraceutical potential of Tacle, suggesting that its extract could be used for dietary supplementation in the treatment of moderate hypercholesterolemia. 相似文献
40.