全文获取类型
收费全文 | 1396篇 |
免费 | 160篇 |
专业分类
1556篇 |
出版年
2023年 | 5篇 |
2022年 | 8篇 |
2021年 | 20篇 |
2020年 | 22篇 |
2019年 | 15篇 |
2018年 | 21篇 |
2017年 | 30篇 |
2016年 | 58篇 |
2015年 | 76篇 |
2014年 | 86篇 |
2013年 | 91篇 |
2012年 | 123篇 |
2011年 | 119篇 |
2010年 | 77篇 |
2009年 | 58篇 |
2008年 | 102篇 |
2007年 | 89篇 |
2006年 | 79篇 |
2005年 | 77篇 |
2004年 | 89篇 |
2003年 | 70篇 |
2002年 | 59篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 12篇 |
1998年 | 19篇 |
1997年 | 17篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 13篇 |
1993年 | 11篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1984年 | 5篇 |
1983年 | 9篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有1556条查询结果,搜索用时 15 毫秒
121.
122.
Almost 10 years ago, microarray technology was established as a new powerful tool for large-scale analysis of gene expression. Soon thereafter the new technology was discovered by toxicologists for the purpose of deciphering the molecular events underlying toxicity, and the term "Toxicogenomics" appeared in scientific literature. Ever since, the toxicology community was fascinated by the multiplicity of sophisticated possibilities toxicogenomics seems to offer: genome-wide analysis of toxicant-induced expression profiles may provide a means for prediction of toxicity prior to classical toxicological endpoints such as histopathology or clinical chemistry. Some researchers even speculated of the classical methods being superfluous before long. It was assumed that by using toxicogenomics it would be possible to classify compounds early in drug development and consequently save animals, time, and money in pre-clinical toxicity studies. Moreover, it seemed within reach to unravel the molecular mechanisms underlying toxicity. The feasibility of bridging data derived from in vitro and in vivo systems, identifying new biomarkers, and comparing toxicological responses "across-species" was also excessively praised. After several years of intensive application of microarray technology in the field of toxicology, not only by the pharmaceutical industry, it is now time to survey its achievements and to question how many of these wishes and promises have really come true. 相似文献
123.
Carotenoid biosynthesis was examined in a phylloplane yeast identified by ITS, 18S and 28S rDNA analysis as a Dioszegia sp. close to D. takashimae. In well-aerated flask or fermentor cultures, this strain produced essentially a single pigment confirmed as the xanthophyll plectaniaxanthin by NMR analysis, at concentrations of 103-175 microgg(-1) biomass dry weight. Detailed studies showed increases in plectaniaxanthin concentrations in the presence of 5 mM hydrogen peroxide (1.8-fold), 50 and 100 microM duroquinone (3.1- and 3.7-fold, respectively), and 2% ethanol (4.9-fold). Whereas oxidative stress is known to enhance the biosynthesis of torularhodin or astaxanthin in other red yeasts where they are associated with an antioxidant function, this is the first report implicating plectaniaxanthin in a similar role. At reduced aeration, biosynthesis of plectaniaxanthin was suppressed and its putative precursor gamma-carotene accumulated. The carotenoid cyclase inhibitor nicotine (5-20 mM) inhibited plectaniaxanthin formation, with lycopene accumulating stoichiometrically. Hydroxy groups at C-1' and C-2' therefore seem to be introduced late in plectaniaxanthin biosynthesis, following cyclization of the beta-ionone ring. 相似文献
124.
125.
Reinhold D Bank U Entz D Goihl A Stoye D Wrenger S Brocke S Thielitz A Stefin S Nordhoff K Heimburg A Täger M Ansorge S 《Biological chemistry》2011,392(3):233-237
Cellular dipeptidyl peptidase IV (DP IV, CD26) and amino-peptidase N (APN, CD13) play regulatory roles in T cell activation and represent potential targets for treatment of inflammatory disorders. We have developed a novel therapeutic strategy, 'peptidase-targeted Immunoregulation' (PETIR?), which simultaneously targets both cellular DP IV and APN via selective binding sites different from the active sites with a single inhibitor. To prove the therapeutic concept of PETIR? in autoimmunity of the central nervous system (CNS), we evaluated the effect of a single substance, PETIR-001, in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. Administration of PETIR-001 significantly delayed and decreased clinical signs of active EAE, when given in a therapeutic manner intraperitoneally from day 15 to day 24 after induction of EAE. Both the acute phase and the first relapse of EAE were markedly inhibited. Importantly, a similar therapeutic benefit was obtained after oral administration of PETIR-001 from day 12 to day 21 after disease induction. Our results demonstrate that PETIR-001 exhibits a therapeutic effect on EAE in SJL/J mice. Thus, PETIR? represents a novel and efficient therapeutic approach for immunotherapy of CNS inflammation. 相似文献
126.
127.
Alexandru Milcu Christiane Roscher Arthur Gessler Dörte Bachmann Annette Gockele Markus Guderle Damien Landais Clément Piel Christophe Escape Sebastien Devidal Olivier Ravel Nina Buchmann Gerd Gleixner Anke Hildebrandt Jacques Roy 《Ecology letters》2014,17(4):435-444
Little is known about the role of plant functional diversity for ecosystem‐level carbon (C) fluxes. To fill this knowledge gap, we translocated monoliths hosting communities with four and 16 sown species from a long‐term grassland biodiversity experiment (‘The Jena Experiment’) into a controlled environment facility for ecosystem research (Ecotron). This allowed quantifying the effects of plant diversity on ecosystem C fluxes as well as three parameters of C uptake efficiency (water and nitrogen use efficiencies and apparent quantum yield). By combining data on ecosystem C fluxes with vegetation structure and functional trait‐based predictors, we found that increasing plant species and functional diversity led to higher gross and net ecosystem C uptake rates. Path analyses and light response curves unravelled the diversity of leaf nitrogen concentration in the canopy as a key functional predictor of C fluxes, either directly or indirectly via LAI and aboveground biomass. 相似文献
128.
129.
Gra?yna Domańska Christian Motz Michael Meinecke Anke Harsman Panagiotis Papatheodorou Boris Reljic Elke A. Dian-Lothrop Antoine Galmiche Oliver Kepp Lars Becker Kathrin Günnewig Richard Wagner Joachim Rassow 《PLoS pathogens》2010,6(4)
The vacuolating toxin VacA, released by Helicobacter pylori, is an important virulence factor in the pathogenesis of gastritis and gastroduodenal ulcers. VacA contains two subunits: The p58 subunit mediates entry into target cells, and the p34 subunit mediates targeting to mitochondria and is essential for toxicity. In this study we found that targeting to mitochondria is dependent on a unique signal sequence of 32 uncharged amino acid residues at the p34 N-terminus. Mitochondrial import of p34 is mediated by the import receptor Tom20 and the import channel of the outer membrane TOM complex, leading to insertion of p34 into the mitochondrial inner membrane. p34 assembles in homo-hexamers of extraordinary high stability. CD spectra of the purified protein indicate a content of >40% β-strands, similar to pore-forming β-barrel proteins. p34 forms an anion channel with a conductivity of about 12 pS in 1.5 M KCl buffer. Oligomerization and channel formation are independent both of the 32 uncharged N-terminal residues and of the p58 subunit of the toxin. The conductivity is efficiently blocked by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), a reagent known to inhibit VacA-mediated apoptosis. We conclude that p34 essentially acts as a small pore-forming toxin, targeted to the mitochondrial inner membrane by a special hydrophobic N-terminal signal. 相似文献
130.
Noam Zelcer Laura J. Sharpe Anke Loregger Ika Kristiana Emma C. L. Cook Lisa Phan Julian Stevenson Andrew J. Brown 《Molecular and cellular biology》2014,34(7):1262-1270
The mevalonate pathway is used by cells to produce sterol and nonsterol metabolites and is subject to tight metabolic regulation. We recently reported that squalene monooxygenase (SM), an enzyme controlling a rate-limiting step in cholesterol biosynthesis, is subject to cholesterol-dependent proteasomal degradation. However, the E3-ubiquitin (E3) ligase mediating this effect was not established. Using a candidate approach, we identify the E3 ligase membrane-associated RING finger 6 (MARCH6, also known as TEB4) as the ligase controlling degradation of SM. We find that MARCH6 and SM physically interact, and consistent with MARCH6 acting as an E3 ligase, its overexpression reduces SM abundance in a RING-dependent manner. Reciprocally, knockdown of MARCH6 increases the level of SM protein and prevents its cholesterol-regulated degradation. Additionally, this increases cell-associated SM activity but is unexpectedly accompanied by increased flux upstream of SM. Prompted by this observation, we found that knockdown of MARCH6 also controls the level of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) in hepatocytes and model cell lines. In conclusion, MARCH6 controls abundance of both SM and HMGCR, establishing it as a major regulator of flux through the cholesterol synthesis pathway. 相似文献