全文获取类型
收费全文 | 3971篇 |
免费 | 234篇 |
国内免费 | 1篇 |
出版年
2022年 | 18篇 |
2021年 | 33篇 |
2020年 | 21篇 |
2019年 | 36篇 |
2018年 | 55篇 |
2017年 | 54篇 |
2016年 | 84篇 |
2015年 | 139篇 |
2014年 | 132篇 |
2013年 | 280篇 |
2012年 | 240篇 |
2011年 | 238篇 |
2010年 | 157篇 |
2009年 | 140篇 |
2008年 | 211篇 |
2007年 | 221篇 |
2006年 | 228篇 |
2005年 | 217篇 |
2004年 | 158篇 |
2003年 | 195篇 |
2002年 | 159篇 |
2001年 | 94篇 |
2000年 | 107篇 |
1999年 | 87篇 |
1998年 | 57篇 |
1997年 | 46篇 |
1996年 | 48篇 |
1995年 | 54篇 |
1994年 | 31篇 |
1993年 | 27篇 |
1992年 | 48篇 |
1991年 | 52篇 |
1990年 | 45篇 |
1989年 | 42篇 |
1988年 | 38篇 |
1987年 | 30篇 |
1986年 | 31篇 |
1985年 | 36篇 |
1984年 | 27篇 |
1983年 | 28篇 |
1982年 | 21篇 |
1981年 | 19篇 |
1980年 | 20篇 |
1979年 | 18篇 |
1978年 | 17篇 |
1976年 | 22篇 |
1975年 | 19篇 |
1974年 | 19篇 |
1973年 | 12篇 |
1968年 | 16篇 |
排序方式: 共有4206条查询结果,搜索用时 0 毫秒
991.
992.
The ability of nutrients to regulate specific metabolic pathways is often overshadowed by their role in basic sustenance. Consequently, the mechanisms whereby these nutrients protect against or promote a variety of acquired metabolic syndromes remains poorly understood. Premenopausal women are generally protected from the adverse effects of obesity despite having a greater proportion of body fat than men. Menopause is often associated with a transformation in body fat morphology and a gradual increase in the susceptibility to metabolic complications, eventually reaching the point where women and men are at equal risk. These phenomena are not explained solely by changes in food preference or nutrient intake suggesting an important role for the sex hormones in regulating the metabolic fate of nutrients and protecting against metabolic disease pathophysiology. Here, we discuss how differences in the acquisition, trafficking, and subceullular metabolism of fats and other lipid soluble nutrients in major organ systems can create overt sex-specific phenotypes, modulate metabolic disease risk, and contribute to the rise in obesity in the modern sedentary climate. Identifying the molecular mechanisms underpinning sex differences in fat metabolism requires the unravelling of the interactions among sex chromosome effects, the hormonal milieu, and diet composition. Understanding the mechanisms that give rise to sex differences in metabolism will help to rationalize treatment strategies for the management of sex-specific metabolic disease risk factors. 相似文献
993.
994.
995.
Teer JK Machida YJ Labit H Novac O Hyrien O Marheineke K Zannis-Hadjopoulos M Dutta A 《The Journal of biological chemistry》2006,281(10):6253-6260
The Origin Recognition Complex (ORC) is a critical component of replication initiation. We have previously reported generation of an Orc2 hypomorph cell line (Delta/-) that expresses very low levels of Orc2 but is viable. We have shown here that Chk2 is phosphorylated, suggesting that DNA damage checkpoint pathways are activated. p53 was inactivated during the derivation of the Orc2 hypomorphic cell lines, accounting for their survival despite active Chk2. These cells also show a defect in the G1 to S-phase transition. Cdk2 kinase activation in G1 is decreased due to decreased Cyclin E levels, preventing progression into S-phase. Molecular combing of bromodeoxyuridine-labeled DNA revealed that once the Orc2 hypomorphic cells enter S-phase, fork density and fork progression are approximately comparable with wild type cells. Therefore, the low level of Orc2 hinders normal cell cycle progression by delaying the activation of G1 cyclin-dependent kinases. The results suggest that hypomorphic mutations in initiation factor genes may be particularly deleterious in cancers with mutant p53 or increased activity of Cyclin E/Cdk2. 相似文献
996.
Kitada S Abe Y Shimada H Kusaka Y Matsuo Y Katayama H Okumura S Akao T Mizuki E Kuge O Sasaguri Y Ohba M Ito A 《The Journal of biological chemistry》2006,281(36):26350-26360
Parasporin-2, a new crystal protein derived from noninsecticidal and nonhemolytic Bacillus thuringiensis, recognizes and kills human liver and colon cancer cells as well as some classes of human cultured cells. Here we report that a potent proteinase K-resistant parasporin-2 toxin shows specific binding to and a variety of cytocidal effects against human hepatocyte cancer cells. Cleavage of the N-terminal region of parasporin-2 was essential for the toxin activity, whereas C-terminal digestion was required for rapid cell injury. Protease-activated parasporin-2 induced remarkable morphological alterations, cell blebbing, cytoskeletal alterations, and mitochondrial and endoplasmic reticulum fragmentation. The plasma membrane permeability was increased immediately after the toxin treatment and most of the cytoplasmic proteins leaked from the cells, whereas mitochondrial and endoplasmic reticulum proteins remained in the intoxicated cells. Parasporin-2 selectively bound to cancer cells in slices of liver tumor tissues and susceptible human cultured cells and became localized in the plasma membrane until the cells were damaged. Thus, parasporin-2 acts as a cytolysin that permeabilizes the plasma membrane with target cell specificity and subsequently induces cell decay. 相似文献
997.
998.
Dark-operative protochlorophyllide reductase (DPOR) in bacteriochlorophyll biosynthesis is a nitrogenase-like enzyme consisting of L-protein (BchL-dimer) as a reductase component and NB-protein (BchN-BchB-heterotetramer) as a catalytic component. Metallocenters of DPOR have not been identified. Here we report that L-protein has an oxygen-sensitive [4Fe-4S] cluster similar to nitrogenase Fe protein. Purified L-protein from Rhodobacter capsulatus showed absorption spectra and an electron paramagnetic resonance signal indicative of a [4Fe-4S] cluster. The activity quickly disappeared upon exposure to air with a half-life of 20s. These results suggest that the electron transfer mechanism is conserved in nitrogenase Fe protein and DPOR L-protein. 相似文献
999.
Yamada T Maruyama M Fujita T Miyabayashi K Shinoda C Kawagishi Y Fujishita T Hayashi R Miwa T Arai N Matsui S Sugiyama E Kobayashi M 《FEBS letters》2006,580(18):4387-4391
Ionizing radiation (IR) is known to upregulate cell surface Fas through p53 activation in various cells. However, the signaling pathway intermediating between p53 activation and cell surface Fas upregulation remains to be elucidated. Recently, Fas-associated phosphatase-1 (FAP-1) has been reported to associate with Fas and inhibit cell surface Fas expression. We evaluated the expression of FAP-1 mRNA following IR in A549 cells. Ionizing radiation inhibited the expression of FAP-1 mRNA. Pretreatment with p53 inhibitor pifithrin alpha cancelled the IR-induced downregulation of FAP-1 mRNA. These results suggest that IR-induced p53 activation may upregulate cell surface Fas via the down-modulation of FAP-1. 相似文献
1000.
Nakajima Y Furuichi Y Biswas KK Hashiguchi T Kawahara K Yamaji K Uchimura T Izumi Y Maruyama I 《FEBS letters》2006,580(2):613-619
Anandamide (AEA) exhibits anti-inflammatory effects. However, its role in the periodontal field remains unknown. Here, we found that gingival crevicular fluid contained a detectable level of AEA. The cannabinoid receptors CB1 and CB2 were expressed by human gingival fibroblasts (HGFs), and markedly upregulated under pathological conditions. AEA significantly reduced the production of pro-inflammatory mediators (IL-6, IL-8 and MCP-1) induced by Porphyromonas gingivalis LPS in HGFs, and this effect was attenuated by AM251 and SR144528, selective antagonists of CB1 and CB2, respectively. Moreover, AEA completely blocked LPS-triggered NF-kappaB activation, implying that AEA may regulate hyperinflammatory reactions in periodontitis. 相似文献