全文获取类型
收费全文 | 5795篇 |
免费 | 378篇 |
国内免费 | 358篇 |
出版年
2024年 | 12篇 |
2023年 | 81篇 |
2022年 | 167篇 |
2021年 | 303篇 |
2020年 | 170篇 |
2019年 | 209篇 |
2018年 | 237篇 |
2017年 | 177篇 |
2016年 | 228篇 |
2015年 | 361篇 |
2014年 | 390篇 |
2013年 | 496篇 |
2012年 | 555篇 |
2011年 | 431篇 |
2010年 | 279篇 |
2009年 | 248篇 |
2008年 | 254篇 |
2007年 | 251篇 |
2006年 | 236篇 |
2005年 | 218篇 |
2004年 | 142篇 |
2003年 | 117篇 |
2002年 | 118篇 |
2001年 | 118篇 |
2000年 | 91篇 |
1999年 | 120篇 |
1998年 | 57篇 |
1997年 | 63篇 |
1996年 | 53篇 |
1995年 | 30篇 |
1994年 | 37篇 |
1993年 | 31篇 |
1992年 | 41篇 |
1991年 | 35篇 |
1990年 | 29篇 |
1989年 | 23篇 |
1988年 | 20篇 |
1987年 | 14篇 |
1986年 | 20篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 11篇 |
1980年 | 4篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1972年 | 3篇 |
1969年 | 2篇 |
排序方式: 共有6531条查询结果,搜索用时 31 毫秒
181.
Jing Chen Cheng-Shi Jiang Wen-Quan Ma Li-Xin Gao Jing-Xu Gong Jing-Ya Li Jia Li Yue-Wei Guo 《Bioorganic & medicinal chemistry letters》2013,23(18):5061-5065
Bruguiesulfurol (1), a cyclic 4-hydroxy-dithiosulfonate isolated from mangrove plant Bruguiera gymnorrhiza, was concisely synthesized for the first time in four steps, and a series of its synthetic derivatives were evaluated for in vitro inhibitory effects on PTP1B and related PTPs. Some derivatives were found to have improved pharmacological profile compared with hit 1. Among them, 5a showed the potent selectivity towards PTP1B over other PTPs, including TCPTP, and 7j exhibited the strongest PTP1B inhibitory activity with an IC50 value of 4.54 μM. 相似文献
182.
183.
Xiao-Zhi Yang Xiao-Juan Diao Wen-Hui Yang Feng Li Guang-Wei He Guo-Qing Gong Yun-Gen Xu 《Bioorganic & medicinal chemistry letters》2013,23(7):2089-2092
A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50 = 3.7 ± 1.0 μmol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50 = 7.8 ± 1.5 μmol/kg). 相似文献
184.
Qian-Ru Du Dong-Dong Li Ya-Zhou Pi Jing-Ran Li Jian Sun Fei Fang Wei-Qing Zhong Hai-Bin Gong Hai-Liang Zhu 《Bioorganic & medicinal chemistry》2013,21(8):2286-2297
A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9–44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56–3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study. 相似文献
185.
内皮祖细胞对于维持血管内皮完整性和血管稳态具有重要作用.增强EPC的数量和功能可使心血管疾病患者获益.炎症、氧化应激对内皮祖细胞动员及其功能发挥具有重要影响,本文着重综述炎症和氧化应激对内皮祖细胞动员的调控,并探讨增进内皮祖细胞数量和功能的相关治疗策略. 相似文献
186.
目的 观察扬子鳄纹状体内乙酰胆碱酯酶(acetylcholinesterase,AChE)和生长抑素信使核糖核酸(somatostatin messenger ribonucleic acid,SOMmRNA)阳性神经元的形态和分布.方法 采用亚铁氰化酮法和原位杂交法观察扬子鳄纹状体内AChE和SOMmRNA阳性神经元的分布和特征.结果 扬子鳄纹状体内有AChE和SOMmRNA阳性神经元分布,两种神经元均有大、中、小型细胞,以中、小型细胞为主,神经元胞体呈圆形、椭圆形、三角形、梭形和多角形.结论 扬子鳄纹状体内有AChE和SOMmRNA阳性神经元分布. 相似文献
187.
We developed a highly sensitive flow injection/amperometric biosensor for the detection of organophosphate pesticides (OPs) using layered double hydroxides (LDHs) as the immobilization matrix of acetylcholinesterase (AChE). LDHs provided a biocompatible microenvironment to keep the bioactivity of AChE, due to the intrinsic properties of LDHs (such as a regular structure, good mechanical, chemical and thermal stabilities, and swelling properties). By integrating the flow injection analysis (FIA) with amperometric detection, the resulting AChE-LDHs modified electrode greatly catalyzed the oxidation of the enzymatically generated thiocholine product, and facilitated the detection automation, thus increasing the detection sensitivity. The analytical conditions for the FIA/amperometric detection of OPs were optimized by using methyl parathion (MP) as a model. The inhibition of MP was proportional to its concentration ranging from 0.005 to 0.3μgmL(-1) and 0.3 to 4.0μgmL(-1) with a detection limit 0.6ngmL(-1) (S/N=3). The developed biosensor exhibited good reproducibility and acceptable stability. 相似文献
188.
An integrated view of bacterial and archaeal diversity in saline soil habitats is essential for understanding the biological and ecological processes and exploiting potential of microbial resources from such environments. This study examined the collective bacterial and archaeal diversity in saline soils using a meta-analysis approach. All available 16S rDNA sequences recovered from saline soils were retrieved from publicly available databases and subjected to phylogenetic and statistical analyses. A total of 9,043 bacterial and 1,039 archaeal sequences, each longer than 250 bp, were examined. The bacterial sequences were assigned into 5,784 operational taxonomic units (OTUs, based on ≥97 % sequence identity), representing 24 known bacterial phyla, with Proteobacteria (44.9 %), Actinobacteria (12.3 %), Firmicutes (10.4 %), Acidobacteria (9.0 %), Bacteroidetes (6.8 %), and Chloroflexi (5.9 %) being predominant. Lysobacter (12.8 %) was the dominant bacterial genus in saline soils, followed by Sphingomonas (4.5 %), Halomonas (2.5 %), and Gemmatimonas (2.5 %). Archaeal sequences were assigned to 602 OTUs, primarily from the phyla Euryarchaeota (88.7 %) and Crenarchaeota (11.3 %). Halorubrum and Thermofilum were the dominant archaeal genera in saline soils. Rarefaction analysis indicated that less than 25 % of bacterial diversity, and approximately 50 % of archaeal diversity, in saline soil habitats has been sampled. This analysis of the global bacterial and archaeal diversity in saline soil habitats can guide future studies to further examine the microbial diversity of saline soils. 相似文献
189.
Polyubiquitin genes from seven ciliate species were amplified, cloned and sequenced. It is estimated that Strombidium sulcatum, Euplotes vannus, E. rariseta and Anteholosticha manca have a polyubiquitin gene of 3 repeats, and A. parawarreni, Paramecium caudatum and Pseudokeronopsis flava 4 repeats. The newly obtained ubiquitins mostly differ from that of humans by 1–5 residues in amino acid sequences. A neighbor-joining tree constructed based on monomeric ubiquitin genes supports the monophyly of an assemblage comprising the litostomateans and some oligohymenophoreans, but not the class Spirotrichea. The monomers from the same species are generally placed together and highly supported for the class Litostomatea, the genera Paramecium and Ichthyophthirius, but not for other species. The non-synonymous/synonymous rate ratio (dN/dS) at the protein level are less than 1, and the synonymous nucleotide differences per synonymous site (pS) from intraspecific comparisons are fairly high (0.02–0.72). These results indicate that ciliates have not only the conserved, but also some quite divergent, polyubiquitin genes and confirm that the polyubiquitin genes in ciliates evolve according to the birth-and-death mode of evolution under strong purifying selection. 相似文献
190.
Sha Wang Wei-Jie Zhao Huihui Liu Haipeng Gong Yong-Bin Yan 《生物化学与生物物理学报:疾病的分子基础》2013,1832(2):302-311
Congenital hereditary cataract, which is mainly caused by the deposition of crystallins in light-scattering particles, is one of the leading causes of newborn blindness in human beings. Recently, an autosomal dominant congenital cataract-microcornea syndrome in a Chinese family has been associated with the S129R mutation in βB1-crystallin. To investigate the underlying molecular mechanism, we examined the effect of the mutation on βB1-crystallin structure and thermal stability. Biophysical experiments indicated that the mutation impaired the oligomerization of βB1-crystallin and shifted the dimer–monomer equilibrium to monomer. Molecular dynamic simulations revealed that the mutation altered the hydrogen-bonding network and hydrophobic interactions in the subunit interface of the dimeric protein, which resulted in the opening of the tightly associated interacting sites to allow the infiltration of the solvent molecules into the interface. Despite the disruption of βB1-crystallin assembly, the thermal stability of βB1-crystallin was increased by the mutation accompanied by the reduction of thermal aggregation at high temperatures. Further analysis indicated that the mutation significantly increased the sensitivity of βB1-crystallin to trypsin hydrolysis. The digested fragments of the mutant were prone to aggregate and unable to protect βA3-crystallin against aggregation. These results indicated that the thermal stability-beneficial mutation S129R in βB1-crystallin provided an excellent model for discovering molecular mechanisms apart from solubility and stability. Our results also highlighted that the increased sensitivity of mutated crystallins towards proteases might play a crucial role in the pathogenesis of congenital hereditary cataract and associated syndrome. 相似文献