全文获取类型
收费全文 | 4853篇 |
免费 | 753篇 |
国内免费 | 406篇 |
专业分类
化学 | 5191篇 |
晶体学 | 28篇 |
力学 | 17篇 |
综合类 | 92篇 |
数学 | 40篇 |
物理学 | 644篇 |
出版年
2024年 | 2篇 |
2023年 | 76篇 |
2022年 | 132篇 |
2021年 | 278篇 |
2020年 | 324篇 |
2019年 | 192篇 |
2018年 | 179篇 |
2017年 | 172篇 |
2016年 | 290篇 |
2015年 | 287篇 |
2014年 | 304篇 |
2013年 | 381篇 |
2012年 | 381篇 |
2011年 | 295篇 |
2010年 | 298篇 |
2009年 | 358篇 |
2008年 | 293篇 |
2007年 | 266篇 |
2006年 | 263篇 |
2005年 | 245篇 |
2004年 | 220篇 |
2003年 | 154篇 |
2002年 | 96篇 |
2001年 | 78篇 |
2000年 | 69篇 |
1999年 | 85篇 |
1998年 | 59篇 |
1997年 | 54篇 |
1996年 | 31篇 |
1995年 | 29篇 |
1994年 | 27篇 |
1993年 | 20篇 |
1992年 | 18篇 |
1991年 | 14篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1986年 | 10篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1978年 | 1篇 |
排序方式: 共有6012条查询结果,搜索用时 160 毫秒
11.
Elisa Martinelli Elisa Guazzelli Cristina Bartoli Matteo Gazzarri Federica Chiellini Giancarlo Galli Maureen E. Callow James A. Callow John A. Finlay Sophie Hill 《Journal of polymer science. Part A, Polymer chemistry》2015,53(10):1213-1225
Well‐defined amphiphilic pentablock copolymers Siy‐(EGx‐FAz)2 composed of polysiloxane (Si), polyethylene glycol (EG), and perfluorohexylethyl polyacrylate (FA) blocks are synthesized by ATRP of FA monomer starting from a difunctional bromo‐terminated macroinitiator. Diblock copolymers EGx‐FAz are also synthesized as model systems. The block copolymers are used, either alone or blended with a PDMS matrix in varied loadings, to prepare antibiofouling coatings. Angle‐resolved XPS and contact angle measurements show that the coating surface is highly enriched in fluorine content but undergoes reconstruction after contact with water. Protein adsorption experiments with human serum albumin and calf serum highlight that diblock copolymers resist protein adhesion better than do pentablock copolymers. Blending of the pentablock copolymer with PDMS results in increased protein adsorption. By contrast, the PDMS‐matrix coatings show high removal percentages of sporelings of the green fouling alga Ulva linza. © 2015 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 2015 , 53, 1213–1225 相似文献
12.
The analysis of vitamin D status, with special emphasis on 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, is gaining interest in clinical studies due to the classical and non-classical effects attributed to this prohormone. In this research, the influence of the two steps preceding determination (viz. sample collection and preparation) on the quantitative analysis of vitamin D and its more important metabolites has been studied. Two preparation approaches, deproteination and solid-phase extraction (SPE), have been evaluated in terms of sensitivity to delimit their application, thus establishing that detection of 1,25-dihydroxyvitamin D cannot be addressed by protein precipitation. Concerning sample collection, serum and plasma reported high accuracy (above 83.3%) for vitamin D and metabolites, while precision, expressed as relative standard deviation, was below 12.9% for all analytes in both samples. Statistical analysis revealed that serum and plasma provided similar physiological levels for vitamin D3, 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, while significantly different levels were obtained for 1,25-dihydroxyvitamin D3, always higher in plasma than in serum. Sample collection and treatment have proved to be significant in the analysis of vitamin D and its relevant metabolites. 相似文献
13.
Maia I. Kelly Tyler J. Bechtel D. Rajasekhar Reddy Erome D. Hankore Jon R. BeckCliff I. Stains 《Analytica chimica acta》2015
Inhibitors of Rho-associated protein kinase (ROCK) enzymatic activity have been shown to reduce the invasive phenotype observed in metastatic hepatocellular carcinoma (HCC). We describe the design, synthesis, and evaluation of a direct probe for ROCK activity utilizing a phosphorylation-sensitive sulfonamido-oxine fluorophore, termed Sox. The Sox fluorophore undergoes an increase in fluorescence upon phosphorylation of a proximal amino acid via chelation-enhanced fluorescence (CHEF, ex. = 360 nm and em. = 485 nm), allowing for the direct visualization of the rate of phosphate addition to a peptide substrate over time. Our optimal probe design, ROCK-S1, is capable of sensitively reporting ROCK activity with a limit of detection of 10 pM and a high degree of reproducibility (Z’-factor = 0.6 at 100 pM ROCK2). As a proof-of-principle for high-throughput screening (HTS) we demonstrate the ability to rapidly assess the efficacy of a 78 member, small molecule library against ROCK2 using a robotics platform. We identify two previously unreported ROCK2 inhibitor scaffolds, PHA665752 and IKK16, with IC50 values of 3.6 μM and 247 nM respectively. Lastly, we define conditions for selectively monitoring ROCK activity in the presence of potential off-target enzymes (PKCα, PKA, and PAK) with similar substrate specificities. 相似文献
14.
In this paper, we have established methylenebis (4-hydroxy-2H-chromen-2-one) as a promising anticancer scaffold with kinesin spindle protein (KSP) inhibitory activity under malignant condition. A series of biscoumarin derivatives (MN1 to MN30) with different substituent were synthesized, and their anticancer activity was explored. Six biscoumarin derivatives that were found active were further selected to formulate organic nanoparticles (ONPs). Anticancer activity of both the forms (viz conventional and ONPs) was compared. MN30 was found most potent whereby MN10 showed good anticancer activity in both, i.e., conventional and ONP form; the structural activity relationship (SAR) study has been established. Computational investigation revealed biscoumarin scaffold as a suitable pharmacophore to bind against KSP protein. Molecular dynamics simulation studies revealed protein-ligand stability and dynamic behavior of biscoumarin-KSP complex. Finally, accruing signal transduction model was formulated to explain the observed MTT trend of conventional and ONP form. The model seems useful towards solving population specific varied results of chemotherapeutic agents. According to the model, MN10 and MN30 derivatives have good pharmacodynamics inertia and therefore, both the molecules were able to provide dose-dependent cytotoxic results. 相似文献
15.
Monomeric sarcosine oxidase (mSOx) fusion with the silaffin peptide, R5, designed previously for easy protein production in low resource areas, was used in a biosilification process to form an enzyme layer electrode biosensor. mSOx is a low activity enzyme (10–20 U/mg) requiring high amounts of enzyme to obtain an amperometric biosensor signal, in the clinically useful range <1 mM sarcosine, especially since the Km is >10 mM. An amperometric biosensor model was fitted to experimental data to investigate dynamic range. mSOx constructs were designed with 6H (6×histidine) and R5 (silaffin) peptide tags and compared with native mSOx. Glutaraldehyde (GA) cross‐linked proteins retained ~5 % activity for mSOx and mSOx‐6H and only 0.5 % for mSOx‐R5. In contrast R5 catalysed biosilification on (3‐mercaptopropyl) trimethoxysilane (MPTMS) and tetramethyl orthosilicate (TMOS) particles created a ‘self‐immobilisation’ matrix retaining 40 % and 76 % activity respectively. The TMOS matrix produced a thick layer (>500 μm) on a glassy carbon electrode with a mediated current due to sarcosine in the clinical range for sarcosinemia (0–1 mM). The mSOx‐R5 fusion protein was also used to catalyse biosilification in the presence of creatinase and creatininase, entrapping all three enzymes. A mediated GC enzyme linked current was obtained with dynamic range available for creatinine determination of 0.1–2 mM for an enzyme layer ~800 nm. 相似文献
16.
Functional Binding Surface of a β‐Hairpin VEGF Receptor Targeting Peptide Determined by NMR Spectroscopy in Living Cells 下载免费PDF全文
Dr. Donatella Diana Anna Russomanno Dr. Lucia De Rosa Dr. Rossella Di Stasi Dr. Domenica Capasso Dr. Sonia Di Gaetano Dr. Alessandra Romanelli Dr. Luigi Russo Dr. Luca D. D'Andrea Prof. Roberto Fattorusso 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(1):91-95
In this study, the functional interaction of HPLW peptide with VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) was determined by using fast 15N‐edited NMR spectroscopic experiments. To this aim, 15N uniformly labelled HPLW has been added to Porcine Aortic Endothelial Cells. The acquisition of isotope‐edited NMR spectroscopic experiments, including 15N relaxation measurements, allowed a precise characterization of the in‐cell HPLW epitope recognized by VEGFR2. 相似文献
17.
18.
Edgardo Becerra Giovanny Aguilera-Durn Laura Berumen Antonio Romo-Mancillas Guadalupe García-Alcocer 《Molecules (Basel, Switzerland)》2021,26(4)
Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy. 相似文献
19.
Francesco Segatta David M. Rogers Naomi T. Dyer Ellen E. Guest Zhuo Li Hainam Do Artur Nenov Marco Garavelli Jonathan D. Hirst 《Molecules (Basel, Switzerland)》2021,26(2)
A fully quantitative theory of the relationship between protein conformation and optical spectroscopy would facilitate deeper insights into biophysical and simulation studies of protein dynamics and folding. In contrast to intense bands in the far-ultraviolet, near-UV bands are much weaker and have been challenging to compute theoretically. We report some advances in the accuracy of calculations in the near-UV, which were realised through the consideration of the vibrational structure of the electronic transitions of aromatic side chains. 相似文献
20.
Nikolay Yanshin Aleksandra Kushnareva Valeriia Lemesheva Claudia Birkemeyer Elena Tarakhovskaya 《Molecules (Basel, Switzerland)》2021,26(9)
Though numerous valuable compounds from red algae already experience high demand in medicine, nutrition, and different branches of industry, these organisms are still recognized as an underexploited resource. This study provides a comprehensive characterization of the chemical composition of 15 Arctic red algal species from the perspective of their practical relevance in medicine and the food industry. We show that several virtually unstudied species may be regarded as promising sources of different valuable metabolites and minerals. Thus, several filamentous ceramialean algae (Ceramium virgatum, Polysiphonia stricta, Savoiea arctica) had total protein content of 20–32% of dry weight, which is comparable to or higher than that of already commercially exploited species (Palmaria palmata, Porphyra sp.). Moreover, ceramialean algae contained high amounts of pigments, macronutrients, and ascorbic acid. Euthora cristata (Gigartinales) accumulated free essential amino acids, taurine, pantothenic acid, and floridoside. Thalli of P. palmata and C. virgatum contained the highest amounts of the nonproteinogenic amino acid β-alanine (9.1 and 3.2 μM g−1 DW, respectively). Several red algae tend to accumulate heavy metals; although this may limit their application in the food industry, it makes them promising candidates for phytoremediation or the use as bioindicators. 相似文献