全文获取类型
收费全文 | 3331篇 |
免费 | 223篇 |
国内免费 | 1篇 |
出版年
2021年 | 27篇 |
2019年 | 22篇 |
2018年 | 29篇 |
2016年 | 50篇 |
2015年 | 71篇 |
2014年 | 83篇 |
2013年 | 146篇 |
2012年 | 167篇 |
2011年 | 157篇 |
2010年 | 97篇 |
2009年 | 86篇 |
2008年 | 173篇 |
2007年 | 151篇 |
2006年 | 151篇 |
2005年 | 127篇 |
2004年 | 129篇 |
2003年 | 137篇 |
2002年 | 130篇 |
2001年 | 32篇 |
2000年 | 29篇 |
1999年 | 36篇 |
1998年 | 38篇 |
1997年 | 39篇 |
1996年 | 34篇 |
1995年 | 54篇 |
1994年 | 31篇 |
1993年 | 44篇 |
1992年 | 22篇 |
1991年 | 20篇 |
1990年 | 24篇 |
1989年 | 26篇 |
1988年 | 21篇 |
1987年 | 23篇 |
1985年 | 16篇 |
1984年 | 30篇 |
1983年 | 26篇 |
1982年 | 21篇 |
1981年 | 38篇 |
1980年 | 22篇 |
1979年 | 23篇 |
1978年 | 41篇 |
1974年 | 15篇 |
1973年 | 27篇 |
1971年 | 15篇 |
1966年 | 22篇 |
1965年 | 18篇 |
1964年 | 19篇 |
1960年 | 16篇 |
1956年 | 24篇 |
1939年 | 18篇 |
排序方式: 共有3555条查询结果,搜索用时 31 毫秒
991.
Alfred Bernard 《Biometals》2004,17(5):519-523
Cadmium (Cd) is cumulative poison which can damage the kidneys after prolonged exposure in the industry or the environment. Renal damage induced by Cd affects primarily the cellular and functional integrity of the proximal tubules, the main site of the renal accumulation of the metal. This results in a variety of urinary abnormalities including an increased excretion of calcium, amino acids, enzymes and proteins. These effects have been documented by a large number of studies conducted during more than two decades in experimental animals and in populations environmentally or occupationally exposed to Cd. There is now a general agreement to say that the most sensitive and specific indicator of Cd-induced renal dysfunction is a decreased tubular reabsorption of low molecular weight proteins, leading to the so-called tubular proteinuria. beta2-microblobulin, retinol-binding protein and alpha1-microglobulin are the microproteins the most commonly used for screening renal damage in populations at risk. Tubular dysfunction develops in a dose-dependent manner according to the internal dose of Cd as assessed on the basis of Cd levels in kidney, urine or in blood. Depending on the sensitivity of the renal biomarker and the susceptibility of the exposed populations, the thresholds of urinary Cd vary from 2 to 10 microg/g creatinine. The thresholds associated with the development of the microproteinuria, the critical effect predictive of a decline of the renal function, is estimated around 10 microg/g creatinine for both occupationally and environmentally exposed populations. Much lower thresholds have been reported in some European studies conducted on the general population. These low thresholds, however, have been derived from associations whose causality remains uncertain and for urinary protein increases that might be reversible. Cd-induced microproteinuria is usually considered as irreversible except at the incipient stage of the intoxication where a partial or complete reversibility has been found in some studies. 相似文献
992.
993.
Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells 下载免费PDF全文
Bared SM Buechler C Boettcher A Dayoub R Sigruener A Grandl M Rudolph C Dada A Schmitz G 《Molecular biology of the cell》2004,15(12):5399-5407
The ATP-binding cassette transporter A1 (ABCA1) facilitates the cellular release of cholesterol and choline-phospholipids to apolipoprotein A-I (apoA-I) and several studies indicate that vesicular transport is associated with ABCA1 function. Syntaxins play a major role in vesicular fusion and have also been demonstrated to interact with members of the ABC-transporter family. Therefore, we focused on the identification of syntaxins that directly interact with ABCA1. The expression of syntaxins and ABCA1 in cultured human monocytes during M-CSF differentiation and cholesterol loading was investigated and syntaxins 3, 6, and 13 were found induced in foam cells together with ABCA1. Immunoprecipitation experiments revealed a direct association of syntaxin 13 and full-length ABCA1, whereas syntaxin 3 and 6 failed to interact with ABCA1. The colocalization of ABCA1 and syntaxin 13 was also shown by immunofluorescence microscopy. Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels and hence to a significant decrease in apoA-I-dependent choline-phospholipid efflux. ABCA1 is localized in Lubrol WX-insoluble raft microdomains in macrophages and syntaxin 13 and flotillin-1 were also detected in these detergent resistant microdomains along with ABCA1. Syntaxin 13, flotillin-1, and ABCA1 were identified as phagosomal proteins, indicating the involvement of the phagosomal compartment in ABCA1-mediated lipid efflux. In addition, the uptake of latex phagobeads by fibroblasts with mutated ABCA1 was enhanced when compared with control cells and the recombinant expression of functional ABCA1 normalized the phagocytosis rate in Tangier fibroblasts. It is concluded that ABCA1 forms a complex with syntaxin 13 and flotillin-1, residing at the plasma membrane and in phagosomes that are partially located in raft microdomains. 相似文献
994.
995.
996.
Although cytokines and cytotoxic T lymphocytes (CTL) are among the predominant mechanisms of host defense against viral pathogens, they can induce an inflammatory response that often leads to tissue injury. Hepatitis C virus (HCV) infection, a major cause of liver-related disease, results in the induction of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and CTL activity, followed by liver injury. Although inflammation facilitates the wound healing process, chronic persistence over several decades results in scar accumulation, fibrosis and often cirrhosis. This review summarizes biological data implicating a cause-and-effect relationship between TNF-alpha levels and the progression of fibrosis in chronic HCV infections, in contrast to the role of TNF-alpha in hepatitis B virus infections. Furthermore, an overview of therapeutic approaches to halting the inflammatory cascade in individuals with chronic HCV, including the use of agents to reduce the level of TNF-alpha, is presented. 相似文献
997.
Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis 总被引:4,自引:0,他引:4 下载免费PDF全文
Degradation of certain inhibitor of apoptosis proteins (IAPs) appears to be critical in the initiation of apoptosis, but the factors that regulate their degradation in mammalian cells are unknown. Nrdp1/FLRF is a RING finger-containing ubiquitin ligase that catalyzes degradation of the EGF receptor family member, ErbB3. We show here that Nrdp1 associates with BRUCE/apollon, a 530 kDa membrane-associated IAP, which contains a ubiquitin-carrier protein (E2) domain. In the presence of an exogenous E2, UbcH5c, purified Nrdp1 catalyzes BRUCE ubiquitination. In vivo, overexpression of Nrdp1 promotes ubiquitination and proteasomal degradation of BRUCE. In many cell types, apoptotic stimuli induce proteasomal degradation of BRUCE (but not of XIAP or c-IAP1), and decreasing Nrdp1 levels by RNA interference reduces this loss of BRUCE. Furthermore, decreasing BRUCE content by RNA interference or overexpression of Nrdp1 promotes apoptosis. Thus, BRUCE normally inhibits apoptosis, and Nrdp1 can be important in the initiation of apoptosis by catalyzing ubiquitination and degradation of BRUCE. 相似文献
998.
999.
Effect of prostaglandin E2 and prostaglandin I2 on PDGF-induced proliferation of LI90, a human hepatic stellate cell line 总被引:1,自引:0,他引:1
Hui AY Cheng AS Chan HL Go MY Chan FK Sakata R Ueno T Sata M Sung JJ 《Prostaglandins, leukotrienes, and essential fatty acids》2004,71(5):329-333
Hepatic stellate cells (HSC) are central to liver fibrosis. The eicosanoid pathway and cyclooxygenase-2 (COX-2) may be an important signaling mechanism in HSC. We investigated the role of COX-2, prostaglandin E(2) (PGE(2)) and prostaglandin I(2) (PGI(2)) in proliferation of LI90, an immortalized cell line of HSC. Our results showed that COX-2 was upregulated by platelet-derived growth factor (PDGF), a mitogen in HSC. COX-2 was responsible for the production of PGE(2) and PGI(2) in PDGF-stimulated LI90 cells. Furthermore, we demonstrated that COX-2 and PGE(2) mediated the proliferative response of LI90 to PDGF while synthetic analogue of PGI(2) exhibited anti-proliferative effect. Our findings suggest complex interactions of prostaglandins in liver fibrogenesis. In vivo studies using animal models are needed to elucidate the effect of COX-2 inhibition by non-steroidal anti-inflammatory drugs or COX-2 inhibitor in hepatic fibrosis. 相似文献
1000.
Moll PR Klausegger A Hintner H Reischl W Breitenbach M Richter K 《The Journal of steroid biochemistry and molecular biology》2004,(1-5):261-267
1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2) D(3)) imposes cell cycle block in late G1 phase in cultured human keratinocytes. We wanted to identify early vitamin D target genes using a subtractive screening approach. Human foreskin keratinocytes were grown to about 70% confluence, treated with 2 x 10(-7) M 1alpha,25(OH)(2) D(3) or left untreated and RNA from both populations were isolated after 22h of incubation. cDNA was synthesised and cloned into plasmid vectors. For screening of the libraries, cDNA was amplified in vitro using T7 RNA polymerase and then the amplified RNA (driver, control population) and single stranded cDNA (tester) were used for subtractive hybridisation. Heterohybrids were then separated from single stranded nucleotides using a hydroxyapatite column. The radiolabeled single stranded cDNA was used for screening a colony blot. Positive clones were rescreened, plasmid DNA was isolated and used for verifying the results by Northern blot analysis, using RNA isolated from untreated keratinocytes, as well as RNA isolated after 6h, 12h and 24h of vitamin D treatment. 相似文献