全文获取类型
收费全文 | 3361篇 |
免费 | 189篇 |
出版年
2022年 | 29篇 |
2021年 | 61篇 |
2020年 | 32篇 |
2019年 | 47篇 |
2018年 | 50篇 |
2017年 | 61篇 |
2016年 | 78篇 |
2015年 | 112篇 |
2014年 | 121篇 |
2013年 | 154篇 |
2012年 | 218篇 |
2011年 | 191篇 |
2010年 | 126篇 |
2009年 | 104篇 |
2008年 | 149篇 |
2007年 | 126篇 |
2006年 | 113篇 |
2005年 | 113篇 |
2004年 | 99篇 |
2003年 | 71篇 |
2002年 | 81篇 |
2001年 | 90篇 |
2000年 | 63篇 |
1999年 | 70篇 |
1998年 | 29篇 |
1997年 | 29篇 |
1996年 | 26篇 |
1995年 | 24篇 |
1992年 | 50篇 |
1991年 | 61篇 |
1990年 | 45篇 |
1989年 | 56篇 |
1988年 | 39篇 |
1987年 | 48篇 |
1986年 | 32篇 |
1985年 | 73篇 |
1984年 | 46篇 |
1983年 | 55篇 |
1982年 | 30篇 |
1981年 | 30篇 |
1980年 | 41篇 |
1979年 | 53篇 |
1978年 | 33篇 |
1976年 | 25篇 |
1975年 | 27篇 |
1974年 | 32篇 |
1973年 | 28篇 |
1971年 | 34篇 |
1970年 | 29篇 |
1969年 | 34篇 |
排序方式: 共有3550条查询结果,搜索用时 109 毫秒
221.
Reactive oxygen species (ROS) have been shown to mediate the effects of several growth factors and vasoactive peptides, such as epidermal growth factor, platelet-derived growth factor, and angiotensin II (AII). Endothelin-1 (ET-1) is a vasoactive peptide which also exhibits mitogenic activity in vascular smooth muscle cells (VSMCs), and is believed to contribute to the pathogenesis of vascular abnormalities such as atherosclerosis, hypertension, and restenosis after angioplasty. However, a possible role for ROS generation in mediating the ET-1 response on extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB), and protein tyrosine kinase 2 (Pyk2), key components of the growth-promoting and proliferative signaling pathways, has not been examined in detail. Our aim was to investigate the involvement of ROS in ET-1-mediated activation of ERK1/2, PKB, and Pyk2 in A-10 VSMCs. ET-1 stimulated ERK1/2, PKB, and Pyk2 phosphorylation in a dose- and time-dependent manner. Pretreatment of A-10 VSMCs with diphenyleneiodonium (DPI), an inhibitor of reduced nicotinamide adenine dinucleotide phosphate oxidase, attenuated ET-1-enhanced ERK1/2, PKB, and Pyk2 phosphorylation. In addition, in parallel with an inhibitory effect on the above signaling components, DPI also blocked ET-1-induced protein synthesis. ET-1 was also found to increase ROS production, which was suppressed by DPI treatment. N-Acetylcysteine, a ROS scavenger, exhibited a response similar to that of DPI and inhibited ET-1-stimulated ERK1/2, PKB, and Pyk2 phosphorylation. These results demonstrate that ROS are critical mediators of ET-1-induced signaling events linked to growth-promoting proliferative and hypertrophic pathways in VSMCs. 相似文献
222.
Cecropin A (1-8)-Melittin (1-18) is a synthetic cecropin A-melittin hybrid peptide with leishmanicidal activity. The primary sequence of the peptide is as follows: KWKLPKKIGIGAVLKVLTTGLPALIS-NH2. 1H and 13C 2D NMR techniques were used to deduce the conformational parameters of chemical shift, 3JNHalpha coupling constants, temperature coefficients of NH chemical shifts and the pattern of intra and inter-residue nOe's. NMR studies were carried out in water (pH 6.0) and hexafluoroacetone (HFA). The peptide was found in a beta-pleated structure in water, and in HFA it adopts a right-handed alpha-helix conformation. Solution structures generated using restrained molecular dynamics simulations were refined by Mardigras to R factors ranging from 0.5 to 0.6. 相似文献
223.
An attempt has been made to develop a method by which to determine the chemical fingerprint of Andrographis paniculata (Acanthaceae). High-performance thin layer chromatography (HPTLC) was used to analyse hexane, chloroform, methanol and water extracts of leaves of A. paniculata. A computerised densitometer was applied to the two-dimensional spectrographic image analysis of the HPTLC plates. An HPLC equipped with a photodiode array detector was used for the analyses of these different extracts. The analyses showed that andrographolide and neoandrographolide are absent in the hexane extract but are present in greater amounts in the methanol extract as compared with the other extracts. These chromatograms may serve as a chemical fingerprint of the drug A. paniculata for quality control purposes and in the preparation of formulations based on the drug. 相似文献
224.
225.
Reynolds RC Srivastava S Ross LJ Suling WJ White EL 《Bioorganic & medicinal chemistry letters》2004,14(12):3161-3164
The preparation of a new 2-carbamoyl pteridine, its activity data against FtsZ from M. tuberculosis (Mtb), and in vitro antibacterial data against Mtb strain H37Ra are presented. 相似文献
226.
Anu?Sharma Gyan?Prakash?Srivastava Vineet?K?Sharma Srinivasan?RamachandranEmail author 《BMC bioinformatics》2004,5(1):142
Background
Microarray is a high-throughput technology to study expression of thousands of genes in parallel. A critical aspect of microarray production is the design aimed at space optimization while maximizing the number of gene probes and their replicates to be spotted. 相似文献227.
Srivastava P Schito M Fattah RJ Hara T Hartman T Buckheit RW Turpin JA Inman JK Appella E 《Bioorganic & medicinal chemistry》2004,12(24):6437-6450
A combinatorial chemistry approach was employed to prepare a restricted library of N-substituted S-acyl-2-mercaptobenzamide thioesters. It was shown that many members of this chemotype display anti-HIV activity via their ability to interact with HIV-1, HIV-2, SIV-infected cells, cell-free virus, and chronically and latently infected cells in a manner consistent with targeting of the highly conserved HIV-1 NCp7 zinc fingers. Compounds were initially screened using two different in vitro antiviral assays and evaluated for stability in neutral buffer containing 10% pooled human serum using a spectrophotometric assay. These data revealed that there was no significant correlation between thioester stability and antiviral activity, however, a slight inverse correlation between serum stability and virucidal activity was noted. Based on the virucidal capability and the ability to select lead compounds to inhibit virus expression from latently infected TNF-induced U1 cells, we next determined if these compounds could prevent HIV cell-to-cell transmission. Several thioesters demonstrated potent inhibition of HIV cell-to-cell transmission with EC50 values in the 80–100 nM range. Thus, we have optimized a series of restricted thioesters and provided evidence that serum stability is not required for antiviral activity. Moreover, selected compounds show potential for development as topical microbicides. 相似文献
228.
A series of thiourea derivatives (7-23, 25-27) of 1-aminotetrahydronaphthalene (4) and 1-amino-2-hydroxytetrahydronaphthalene (5) were synthesized in single pot in 48-90% yield and evaluated for their anorexigenic activity. Among them compounds 10, 14, 15, 16 and 22 exhibited significant anorexigenic activity without any antidepressant effect and provided a new structural lead for appetite suppressants. 相似文献
229.
Bhat BA Ponnala S Sahu DP Tiwari P Tripathi BK Srivastava AK 《Bioorganic & medicinal chemistry》2004,12(22):5857-5864
A number of thiazolidine-2,4-diones derivatives having carboxylic ester appendage at N-3 were synthesized and their antihyperglycemic activity was evaluated. Many of these derivatives as well as their corresponding carboxylic acid showed significant improvement on post-prandial hyperglycemia in normal rats, in contrast to their poor agonist activity at PPARgamma. 相似文献
230.
Srivastava N Sangita Ray S Singh MM Dwivedi A Kumar A 《Bioorganic & medicinal chemistry》2004,12(5):1011-1021
Diaryl naphthyl methanes and the corresponding 1, 2, 3, 4- and 5, 6, 7, 8-tetrahydro naphthyl methane derivatives have been synthesized as novel estrogen receptor binding ligands. The secondary and tertiary amino alkoxy derivatives of diaryl naphthyl and tetrahydro naphthyl methane interact with the estrogen receptor to elicit promising estrogenic, antiestrogenic and implantation inhibition activities in rats. The most active compounds in this series are 7, 9 and 20, cent percent active in preventing implantation in rats at 2.5 mgkg(-1) dose. 相似文献