全文获取类型
收费全文 | 11254篇 |
免费 | 921篇 |
国内免费 | 745篇 |
出版年
2024年 | 8篇 |
2023年 | 184篇 |
2022年 | 349篇 |
2021年 | 628篇 |
2020年 | 395篇 |
2019年 | 512篇 |
2018年 | 537篇 |
2017年 | 341篇 |
2016年 | 510篇 |
2015年 | 710篇 |
2014年 | 791篇 |
2013年 | 914篇 |
2012年 | 1067篇 |
2011年 | 928篇 |
2010年 | 571篇 |
2009年 | 495篇 |
2008年 | 533篇 |
2007年 | 492篇 |
2006年 | 427篇 |
2005年 | 361篇 |
2004年 | 302篇 |
2003年 | 225篇 |
2002年 | 187篇 |
2001年 | 202篇 |
2000年 | 170篇 |
1999年 | 174篇 |
1998年 | 101篇 |
1997年 | 123篇 |
1996年 | 105篇 |
1995年 | 87篇 |
1994年 | 91篇 |
1993年 | 48篇 |
1992年 | 74篇 |
1991年 | 55篇 |
1990年 | 44篇 |
1989年 | 46篇 |
1988年 | 38篇 |
1987年 | 27篇 |
1986年 | 19篇 |
1985年 | 22篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 156 毫秒
981.
Lu A Luo H Shi M Wu G Yuan Y Liu J Tang F 《Bioorganic & medicinal chemistry letters》2011,21(16):4924-4927
A series of benzamide derivatives including two scaffolds were designed and synthesized as potential histone deacetylase inhibitors. Most of synthesized compounds showed moderate enzymatic potency at the same order of magnitude, and compound 12b possessed better potency to the positive control (3.8 μM vs 13.0 μM). It also showed a 50-fold increase in vitro anticancer activity against DU-145 cell-lines. Molecular docking studies were carried out and used to explain the structure-activity relationships observed in vitro. Then we found that the cavity surrounded by ASP104, HIS33, PRO34 and PHE155 may be crucial for the inhibitors’ activity. The docking results provide some useful information for future design of more potent inhibitors. 相似文献
982.
A fluorescent fatty acid probe, DAUDA, selectively displaces two myristates bound in human serum albumin 总被引:1,自引:0,他引:1
Wang Y Luo Z Shi X Wang H Nie L Huang M 《Protein science : a publication of the Protein Society》2011,20(12):2095-2101
11-(Dansylamino) undecanoic acid (DAUDA) is a dansyl-type fluorophore and has widely used as a probe to determine the binding site for human serum albumin (HSA). Here, we reported that structure of HSA-Myristate-DAUDA ternary complex and identified clearly the presence of two DAUDA molecules at fatty acid (FA) binding site 6 and 7 of HSA, thus showing these two sites are weak FA binding sites. This result also show that DAUDA is an appropriate probe for FA site 6 and 7 on HSA as previous studied, but not a good probe of FA binding site 1 that is likely bilirubin binding site on HSA. 相似文献
983.
Lü S Luo Q Hao X Li X Ji L Zheng W Wang F 《Bioorganic & medicinal chemistry letters》2011,21(23):6964-6968
Six analogs of imatinib, an Abl kinase inhibitor clinically used as a first-line therapeutic agent for chronic myeloid leukaemia (CML), have been synthesized and characterized. And their potency as Abl kinase inhibitors have been screened by a robust virtual screening method developed based on the crystal structure (PDB code 2hyy) of Abl-imatinib complex using Surflex-Docking. The docking results are consistent with the inhibitory potency of the compounds characterized by MS method. And the H-bonds between imatinib analogs and Thr315 and Met318 residues in Abl kinase are shown to be crucial for achieving accurate poses and high binding affinities for the ATP-competitive kinase inhibitors. 相似文献
984.
Sorption and ecotoxicity of pentachlorophenol polluted sediment amended with rice-straw derived biochar 总被引:4,自引:0,他引:4
To investigate the feasibility of using biochar to control organic pollutants in sediments, we extracted biochar from rice-straw combustion residues (RBC) and studied its adsorption ability and effect on seed germination ecotoxicity of pentachlorophenol (PCP). The results showed that the Freundlich and dual-mode models could describe all the sorption isotherm data well, and the log KOC values increased with increasing RBC content. With 50 mg kg−1 PCP in the sediment, a significant seed growth inhibition (P < 0.01) was observed. The addition of 2.0% RBC lowered the PCP concentration in the extraction liquid from 4.53 to 0.17 mg L−1 and increased the germination rate and root length significantly. Furthermore, it was found that the addition of RBC had no toxic but stimulative effect on root elongation. Consequently, RBC could serve as a potential supersorbent for the remediation of organic pollution in situ. 相似文献
985.
Chen SB Tan JH Ou TM Huang SL An LK Luo HB Li D Gu LQ Huang ZS 《Bioorganic & medicinal chemistry letters》2011,21(3):1004-1009
Discovery of potent and selective ligands for telomeric G-quadruplex DNA is a challenging work. Through a combination approach of pharmacophore model construction, model validation, database virtual screening, chemical synthesis and interaction evaluation, we discovered and confirmed triaryl-substituted imidazole TSIZ01 to be a new telomeric G-quadruplex ligand with potent binding and stabilizing activity to G-quadruplex DNA, as well as a 8.7-fold selectivity towards telomeric G-quadruplex DNA over duplex DNA. 相似文献
986.
Development of insect-resistant transgenic cotton with chimeric TVip3A* accumulating in chloroplasts
An optimized vip3A gene, designated as vip3A* was chemically synthesized and a thi1 gene chloroplast transit peptide coding sequence was attached to its 5′ end to produce the tvip3A*. vip3A* and tvip3A* genes were transformed into Gossypium hirsutum cv. Zhongmiansuo35. Of 42 independent transformants, 36 were positive for the vip3A* or tvip3A* gene. Four independent transgenic T1 lines with single-copy insertions and unchanged phenotypes (CTV1 and CTV2 for tvip3A*, and CV1 and CV2 for vip3A*) were selected by Southern blotting, and subjected to an insect bioassay and field assessment. Four homozygous T2 transgenic
lines were then selected and the amount of expressed Vip3A* protein was determined by western blotting and ELISA. The protein
concentrations of CTV1 and CTV2 were about three-fold higher than those of CV1 and CV2. As expected, the Vip3A* protein of
CTV1 and CTV2 were transported to the chloroplasts, where they accumulated. The Vip3A* protein concentration in the chloroplasts
of CTV1 and CTV2 was about 15-fold of that of CV1 and CV2. All four transgenic lines showed 100% mortality against fall armyworm
(Spodoptera frugiperda) and beet armyworm (Spodoptera exigua) by insect bioassay. Moreover, CTV1 and CTV2 exhibited 100% mortality against cotton bollworm (CBW, Helicoverpa zea), whereas CV1 and CV2 showed 75.0% and 72.5% mortality against CBW, respectively. The field bioassay indicated that CTV1
and CTV2 were more resistant to CBW than CV1 and CV2. Our results suggest that the two tvip3A* transgenic lines (CTV1 and CTV2) can be used to develop insect-resistant cultivars and could be used as a resource for raising
multi-toxins-expressing transgenic cotton. 相似文献
987.
A series of novel benzimidazole derivatives were designed, synthesized, and evaluated for their activities against four kinds of enteroviruses, that is, Coxsackie virus A16, B3, B6 and Enterovirus 71 in VERO cells. Strong activities against enterovirus replication and low cytotoxicities were observed in these benzimidazoles generally. The most promising compound was (l)-2-(pyridin-2-yl)-N-(2-(4-nitrophenyl)pentan-3-yl)-1H-benzimidazole-4-carboxamide (16), with a high antiviral potency (IC(50)=1.76 μg/mL) and a remarkable selectivity index (328). These compounds were selected for further evaluation as novel enterovirus inhibitors. 相似文献
988.
β-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. We first used a structure-based approach to develop 24 new vinylogous carbamates (4a-15a, 4b-15b) that target FabH for the development of new antibiotics in this paper. Potent FabH inhibitory and selective anti- Gram-negative bacteria activities were observed in most of these vinylogous carbamates. Especially, compound 6a and 7a showed the most potent FabH inhibitory activity with IC?? of 2.6 and 3.3 μM, respectively. Docking simulation was performed to position compound 6a into the Escherichia coli FabH active site and the possible binding conformation of compounds has been proposed. The biological data and molecular docking indicated that compounds 6a and 7a were potent inhibitors of E. coli FabH as antibiotics deserving further research. 相似文献
989.
A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitro, with an IC(50) value of 0.8μg/mL. Docking simulation was performed to insert compound 10c into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10c with potent inhibitory activity in tumor growth may be a potential anticancer agent. 相似文献
990.
Yuan M Luo M Song Y Xu Q Wang X Cao Y Bu X Ren Y Hu X 《Bioorganic & medicinal chemistry》2011,19(3):1189-1196
Several recent developments suggest that the human glyoxalase I (GLO I) is a potential target for anti-tumor drug development. In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600μM, 2.600μM, 3.200μM, 3.600μM and 3.600μM, respectively. To elucidate the structural features of potent inhibitors, docking-based three-dimensional structure-activity relationship (3D-QSAR) analyses were performed. Satisfactory agreement between experiment and theory suggests that comparative molecular similarity index analysis (CoMSIA) modeling exhibit much better correlation and predictive power. The cross-validated q(2) value is 0.638 while no-validation r(2) value is 0.930. Integrated with docking-based 3D-QSAR CoMSIA modeling, molecular surface property (electrostatic and steric) mapping and molecular dynamics simulation, a set of receptor-ligand binding models and bio-affinity predictive models for rational design of more potent inhibitors of GLO I are established. 相似文献