全文获取类型
收费全文 | 1862篇 |
免费 | 100篇 |
国内免费 | 1篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 10篇 |
2021年 | 28篇 |
2020年 | 14篇 |
2019年 | 22篇 |
2018年 | 47篇 |
2017年 | 28篇 |
2016年 | 42篇 |
2015年 | 66篇 |
2014年 | 97篇 |
2013年 | 131篇 |
2012年 | 166篇 |
2011年 | 148篇 |
2010年 | 101篇 |
2009年 | 77篇 |
2008年 | 140篇 |
2007年 | 150篇 |
2006年 | 131篇 |
2005年 | 100篇 |
2004年 | 123篇 |
2003年 | 94篇 |
2002年 | 92篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 14篇 |
1998年 | 13篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 10篇 |
1994年 | 9篇 |
1993年 | 4篇 |
1992年 | 13篇 |
1991年 | 4篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有1963条查询结果,搜索用时 453 毫秒
151.
Marcotullio MC Pagiotti R Maltese F Oball-Mond Mwankie GN Hoshino T Obara Y Nakahata N 《Bioorganic & medicinal chemistry》2007,15(8):2878-2882
Two new cyathane diterpenes, cyrneine C (4) and D (5), were isolated from the mushroom Sarcodon cyrneus, along with previously isolated cyrneine A, B and glaucopine C. The structures of the novel diterpenoids were determined by the analysis of spectroscopic data. Effects of the cyrneines and glaucopine C on the NGF gene expression in 1321N1 cells and on neurite outgrowth on PC12 cells were evaluated. 相似文献
152.
153.
N. A. Moltschaniwskyj K. Hall Marek R. Lipinski J. E. A. R. Marian M. Nishiguchi M. Sakai D. J. Shulman B. Sinclair D. L. Sinn M. Staudinger R. Van Gelderen R. Villanueva K. Warnke 《Reviews in Fish Biology and Fisheries》2007,17(2-3):455-476
When using cephalopods as experimental animals, a number of factors, including morality, quality of information derived from
experiments, and public perception, drives the motivation to consider welfare issues. Refinement of methods and techniques
is a major step in ensuring protection of cephalopod welfare in both laboratory and field studies. To this end, existing literature
that provides details of methods used in the collection, handling, maintenance, and culture of a range of cephalopods is a
useful starting point when refining and justifying decisions about animal welfare. This review collates recent literature
in which authors have used cephalopods as experimental animals, revealing the extent of use and diversity of cephalopod species
and techniques. It also highlights several major issues when considering cephalopod welfare; how little is known about disease
in cephalopods and its relationship to senescence and also how to define objective endpoints when animals are stressed or
dying as a result of the experiment. 相似文献
154.
Sakashita H Akahoshi F Yoshida T Kitajima H Hayashi Y Ishii S Takashina Y Tsutsumiuchi R Ono S 《Bioorganic & medicinal chemistry》2007,15(2):641-655
Dipeptidyl peptidase IV (DPP-IV) inhibitors are looked to as a potential new antidiabetic agent class. A series of [(S)-gamma-(arylamino)prolyl]thiazolidine compounds in which the electrophilic nitrile is removed are chemically stable DPP-IV inhibitors. To discover a structure for the gamma-substituent of the proline moiety more suitable for interacting with the S(2) pocket of DPP-IV, optimization focused on the gamma-substituent was carried out. The indoline compound 22e showed a DPP-IV-inhibitory activity 100-fold more potent than that of the prolylthiazolidine 10 and comparable to that of NVP-DPP728. It also displayed improved inhibitory selectivity for DPP-IV over DPP8 and DPP9 compared to compound 10. Indoline compounds such as 22e have a rigid conformation with double restriction of the aromatic moiety by proline and indoline structures to promote interaction with the binding site in the S(2) pocket of DPP-IV. The double restriction effect provides a potent inhibitory activity which compensates for the decrease in activity caused by removing the electrophilic nitrile. 相似文献
155.
TRPM7 is a stretch- and swelling-activated cation channel involved in volume regulation in human epithelial cells 总被引:6,自引:0,他引:6
Stretch- and swelling-activated cation (SSAC) channels play essential roles not only in sensing and transducing external mechanical stresses but also in regulating cell volume in living cells. However, the molecular nature of the SSAC channel has not been clarified. In human epithelial HeLa cells, single-channel recordings in cell-attached and inside-out patches revealed expression of a Mg2+- and Gd3+-sensitive nonselective cation channel that is exquisitely sensitive to membrane stretch. Whole cell recordings revealed that the macroscopic cationic currents exhibit transient receptor potential (TRP) melastatin (TRPM)7-like properties such as outward rectification and sensitivity to Mg2+ and Gd3+. The whole cell cation current was augmented by osmotic cell swelling. RT-PCR and Western blotting demonstrated molecular expression of TRPM7 in HeLa cells. Treatment with small interfering RNA (siRNA) targeted against TRPM7 led to abolition of single stretch-activated cation channel currents and of swelling-activated, whole cell cation currents in HeLa cells. The silencing of TRPM7 by siRNA reduced the rate of cell volume recovery after osmotic swelling. A similar inhibition of regulatory volume decrease was also observed when extracellular Ca2+ was removed or Gd3+ was applied. It is thus concluded that TRPM7 represents the SSAC channel endogenously expressed in HeLa cells and that, by serving as a swelling-induced Ca2+ influx pathway, it plays an important role in cell volume regulation. regulatory volume decrease 相似文献
156.
C-reactive protein suppresses insulin signaling in endothelial cells: role of spleen tyrosine kinase
Although few epidemiological studies have demonstrated that C-reactive protein (CRP) is related to insulin resistance, no study to date has examined the molecular mechanism. Here, we show that recombinant CRP attenuates insulin signaling through the regulation of spleen tyrosine kinase (Syk) on small G-protein RhoA, jun N-terminal kinase (JNK) MAPK, insulin receptor substrate-1 (IRS-1), and endothelial nitric oxide synthase in vascular endothelial cells. Recombinant CRP suppressed insulin-induced NO production, inhibited the phosphorylation of Akt and endothelial nitric oxide synthase, and stimulated the phosphorylation of IRS-1 at the Ser307 site in a dose-dependent manner. These events were blocked by treatment with an inhibitor of RhoA-dependent kinase Y27632, or an inhibitor of JNK SP600125, or the transfection of dominant negative RhoA cDNA. Next, anti-CD64 Fcgamma phagocytic receptor I (FcgammaRI), but not anti-CD16 (FcgammaRIIIa) or anti-CD32 (FcgammaRII) antibody, partially blocked the recombinant CRP-induced phosphorylation of JNK and IRS-1 and restored, to a certain extent, the insulin-stimulated phosphorylation of Akt. Furthermore, we identified that recombinant CRP modulates the phosphorylation of Syk tyrosine kinase in endothelial cells. Piceatannol, an inhibitor of Syk tyrosine kinase, or infection of Syk small interference RNA blocked the recombinant CRP-induced RhoA activity and the phosphorylation of JNK and IRS-1. In addition, piceatannol also restrained CRP-induced endothelin-1 production. We conclude that recombinant CRP induces endothelial insulin resistance and dysfunction, and propose a new mechanism by which recombinant CRP induces the phosphorylation of JNK and IRS-1 at the Ser307 site through a Syk tyrosine kinase and RhoA-activation signaling pathway. 相似文献
157.
Ogawa J Yamanaka H Mano J Doi Y Horinouchi N Kodera T Nio N Smirnov SV Samsonova NN Kozlov YI Shimizu S 《Bioscience, biotechnology, and biochemistry》2007,71(7):1607-1615
Arthrobacter simplex AKU 626 was found to synthesize 4-hydroxyisoleucine from acetaldehyde, alpha-ketobutyrate, and L-glutamate in the presence of Escherichia coli harboring the branched chain amino acid transaminase gene (ilvE) from E. coli K12 substrain MG1655. By using resting cells of A. simplex AKU 626 and E. coli BL21(DE3)/pET-15b-ilvE, 3.2 mM 4-hydroxyisoleucine was produced from 250 mM acetaldehyde, 75 mM alpha-ketobutyrate, and 100 mM L-glutamate with a molar yield to alpha-ketobutyrate of 4.3% in 50 mM Tris-HCl buffer (pH 7.5) containing 2 mM MnCl(2) x 4H(2)O at 28 degrees C for 2 h. An aldolase that catalyzes the aldol condensation of acetaldehyde and alpha-ketobutyrate was purified from A. simplex AKU 626. Mn(2+) and pyridoxal 5'-monophosphate were effective in stabilizing the enzyme. The native and subunit molecular masses of the purified aldolase were about 180 and 32 kDa respectively. The N-terminal amino acid sequence of the purified enzyme showed no significant homology to known aldolases. 相似文献
158.
159.
Holger Maier Christine Schütt Ralph Steinkamp Anja Hurt Elida Schneltzer Philipp Gormanns Christoph Lengger Mark Griffiths David Melvin Neha Agrawal Rafael Alcantara Arthur Evans David Gannon Simon Holroyd Christian Kipp Navis Pretheeba Raj David Richardson Sophie LeBlanc Laurent Vasseur Hiroshi Masuya Kimio Kobayashi Tomohiro Suzuki Nobuhiko Tanaka Shigeharu Wakana Alison Walling David Clary Juan Gallegos Helmut Fuchs Martin Hrabě de Angelis Valerie Gailus-Durner 《Mammalian genome》2015,26(9-10):467-481
160.
Naoki Kubo Hidehiro Toh Kenjiro Shirane Takayuki Shirakawa Hisato Kobayashi Tetsuya Sato Hidetoshi Sone Yasuyuki Sato Shin-ichi Tomizawa Yoshinori Tsurusaki Hiroki Shibata Hirotomo Saitsu Yutaka Suzuki Naomichi Matsumoto Mikita Suyama Tomohiro Kono Kazuyuki Ohbo Hiroyuki Sasaki 《BMC genomics》2015,16(1)