全文获取类型
收费全文 | 476篇 |
免费 | 51篇 |
出版年
2022年 | 6篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 21篇 |
2014年 | 21篇 |
2013年 | 22篇 |
2012年 | 38篇 |
2011年 | 27篇 |
2010年 | 19篇 |
2009年 | 15篇 |
2008年 | 26篇 |
2007年 | 26篇 |
2006年 | 14篇 |
2005年 | 24篇 |
2004年 | 20篇 |
2003年 | 20篇 |
2002年 | 17篇 |
2001年 | 17篇 |
2000年 | 13篇 |
1999年 | 17篇 |
1998年 | 4篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 8篇 |
1991年 | 14篇 |
1990年 | 12篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1981年 | 3篇 |
1979年 | 5篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1973年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有527条查询结果,搜索用时 2 毫秒
341.
Loong AM Hiong KC Wong WP Chew SF Ip YK 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2012,182(2):231-245
This study aimed to identify estivation-specific gene clusters through the determination of differential gene expressions
in the liver of Protopterus annectens after 6 days of estivation in a mucus cocoon in air (normoxia) using suppression subtractive hybridization polymerase chain
reaction. Our results demonstrated that 6 days of estivation in normoxia led to up-regulation of mRNA expressions of several
genes related to urea synthesis, including carbamoyl phosphate synthetase (Cps), argininosuccinate synthetase and glutamine
synthetase. They indicate that increased urea synthesis, despite being energy-intensive, is an important adaptive response
of estivation. They also offer indirect support to the proposition that urea synthesis in this lungfish involved a Cps that
uses glutamine as a substrate. In addition, up- or down-regulation of several gene clusters occurred in the liver of P. annectens after 6 days of estivation in normoxia. These estivation-specific genes were involved in the prevention of clot formation,
activation of the lectin pathway for complement activation, conservation of minerals (e.g. iron and copper) and increased
production of hemoglobin beta. Since there were up- and down-regulation of mRNA expressions of genes related to ribosomal
proteins and translational elongation factors, there could be simultaneous increases in protein degradation and protein synthesis
during the first 6 days (the induction phase) of estivation, confirming the importance of reconstruction of protein structures
in preparation for the maintenance phase of estivation. 相似文献
342.
Yuen K. Ip Ai M. Loong You R. Chng Kum C. Hiong Shit F. Chew 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2012,182(8):1081-1094
The complete cDNA sequence of CPS I obtained from the liver of the hylid tree frog, Litoria caerulea, consisted of 4,485?bp which coded for 1,495 amino acids with an estimated molecular mass of 163.7?kDa. The deduced CPS I consisted of a mitochondrial targeting sequence of 33 amino acid residues, a glutaminase amidotransferase component spanning from tyrosine 95 to leucine 425, and a methylglyoxal synthetase-like component spanning from valine 441 to lysine 1566. It also comprised two cysteine residues (cysteine 1360 and cysteine 1370) that are characteristic of N-acetyl-l-glutamate dependency. Similar to the CPS I of Rana catesbeiana and Cps III of lungfishes and teleosts, it contained the Cys?CHis?CGlu catalytic triad (cysteine 304, histidine 388 and glutamate 390). All Cps III contain methionine 305 and glutamine 308, which are essential for the Cys?CHis?CGlu triad to react with glutamine, but the CPS I of R. catesbeiana contains lysine 305 and glutamate 308, and therefore cannot effectively utilize glutamine as a substrate. However, the CPS I of L. caerulea, unlike that of R. catesbeiana, contained besides glutamate 308, methionine 305 instead of lysine 305, and thus represented a transitional form between Cps III and CPS I. Indeed, CPS I of L. caerulea could utilize glutamine or NH4 + as a substrate in vitro, but the activity obtained with glutamine?+?NH4 + reflected that obtained with NH4 + alone. Furthermore, only?<5?% of the glutamine synthetase activity was present in the hepatic mitochondria, indicating that CPS I of L. caerulea did not have an effective supply of glutamine in vivo. Hence, our results confirmed that the evolution of CPS I from Cps III occurred in amphibians. Since L. caerulea contained high levels of urea in its muscle and liver, which increased significantly in response to desiccation, its CPS I had the dual functions of detoxifying ammonia to urea and producing urea to reduce evaporative water loss. 相似文献
343.
Schuler KL Green DE Justice-Allen AE Jaffe R Cunningham M Thomas NJ Spalding MG Ip HS 《EcoHealth》2012,9(2):163-170
Eurasian collared doves (Streptopelia decaocto) have expanded their range across the United States since their introduction several decades ago. Recent mortality events in Eurasian collared doves in Arizona and Montana, USA, during the winter of 2009-2010 were the result of pigeon paramyxovirus (PPMV), a novel disease agent. The first instance of mortality by this emerging infectious disease in this species occurred in Florida in 2001 with subsequent disease events in 2006 and 2008. Full diagnostic necropsies were performed on carcasses from the three states. PPMV was identified by RT-PCR and virus isolation and was sequenced to the VIb genotype of avian paramyxovirus-1 (APMV). Other APMVs are common in a variety of free-ranging birds, but concern is warranted because of the potential for commingling of this species with native birds, virus evolution, and threats to domestic poultry. Improved surveillance for wildlife mortality events and efforts to prevent introduction of non-native animals could reduce the threat of introducing new pathogens. 相似文献
344.
345.
Cdk5 is a member of the cyclin-dependent kinase family. Unlike other conventional Cdks that are major regulators of eukaryotic cell cycle progression, Cdk5 displays diverse functions in neuronal as well as non-neuronal tissues. In particular, accumulating evidence points to the roles of this kinase in CNS development and other cellular processes. In this article, we summarize the functional roles of Cdk5 pertaining to the formation and functions of synapse, a specialized structure for the fundamental functions of neurons. 相似文献
346.
A novel approach for the treatment of leukemia is the differentiation therapy in which immature leukemia cells are induced to attain a mature phenotype when exposed to differentiation inducers, either alone or in combinations with other chemotherapeutic or chemopreventive drugs. Over the past decade, numerous studies indicated that green tea catechins (GTC) could suppress the growth and induce apoptosis on a number of human cancer cell lines. However, the differentiation-inducing activity of GTC on human tumors remains poorly understood. In the present study, the effect of the major GTC epigallocatechin-3-gallate (EGCG) on the proliferation and differentiation of a human eosinophilc leukemic cell line, EoL-1, was examined. Our results showed that EGCG suppressed the proliferation of the EoL-1 cells in a dose-dependent manner, with an estimated IC(50) value of 31.5 microM. On the other hand, EGCG at a concentration of 40 microM could trigger the EoL-1 cells to undergo morphological differentiation into mature eosinophil-like cells. Using RT-PCR and flow cytometry, it was found that EGCG upregulated the gene and protein expression of two eosinophil-specific granule proteins, the major basic protein (MBP) and eosinophil peroxidase (EPO), in EoL-1 cells. Taken together, our findings suggest that EGCG can exhibit anti-leukemic activity on a human eosinophilic cell line EoL-1 by suppressing the proliferation and by inducing the differentiation of the leukemia cells. 相似文献
347.
Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver 总被引:6,自引:0,他引:6
下载免费PDF全文
![点击此处可从《Cell stress & chaperones》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Tumor necrosis factor-alpha (TNFalpha) could cause apoptosis in hepatic tissue of D-galactosamine sensitized mice, as evidenced by the increase in the extent of DNA fragmentation. The hepatic apoptosis induced by TNFalpha was associated with hepatocellular damage as assessed by plasma alanine aminotransferase activity. Schisandrin B (Sch B) pretreatment at daily doses ranging from 0.5 to 2 mmol/kg for 3 days caused a dose-dependent protection against TNFalpha-induced apoptosis in mice. The hepatoprotection was accompanied by a parallel reduction in the extent of hepatocellular damage. The same Sch B pretreatment regimens increased hepatic Hsp70 level in a dose-dependent manner. The relevance of Sch B-induced increase in Hsp70 expression to the prevention of TNFalpha-triggered hepatic apoptosis remains to be elucidated. 相似文献
348.
349.
Li Q Ching AK Chan BC Chow SK Lim PL Ho TC Ip WK Wong CK Lam CW Lee KK Chan JY Chui YL 《The Journal of biological chemistry》2004,279(50):52106-52116
BRE, brain and reproductive organ-expressed protein, was found previously to bind the intracellular juxtamembrane domain of a ubiquitous death receptor, tumor necrosis factor receptor 1 (TNF-R1), and to down-regulate TNF-alpha-induced activation of NF-kappaB. Here we show that BRE also binds to another death receptor, Fas, and upon overexpression conferred resistance to apoptosis induced by TNF-alpha, anti-Fas agonist antibody, cycloheximide, and a variety of stress-related stimuli. However, down-regulation of the endogenous BRE by small interfering RNA increased apoptosis to TNF-alpha, but nottoetoposide, indicating that the physiological antiapoptotic role of this protein is specific to death receptor-mediated apoptosis. We further demonstrate that BRE mediates antiapoptosis by inhibiting the mitochondrial apoptotic machinery but without translocation to the mitochondria or nucleus or down-regulation of the cellular level of truncated Bid. Dissociation of BRE rapidly from TNF-R1, but not from Fas, upon receptor ligation suggests that this protein interacts with the death inducing signaling complex during apoptotic induction. Increased association of BREwith phosphorylated, sumoylated, and ubiquitinated proteins after death receptor stimulation was also detected. We conclude that in contrast to the truncated Bid that integrates mitochondrial apoptosis to death receptor-triggered apoptotic cascade, BRE inhibits the integration. We propose that BRE inhibits, by ubiquitination-like activity, components in or proximal to the death-inducing signaling complexes that are necessary for activation of the mitochondria. 相似文献
350.
The p38 mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signalling mechanism involved in processes as diverse as apoptosis, cell fate determination, immune function and stress response. Aberrant p38 signalling has been implicated in many human diseases, including heart disease, cancer, arthritis and neurodegenerative diseases. To further understand the role of p38 in these processes, we generated a Drosophila strain that is null for the D-p38a gene. Mutants are homozygous viable and show no observable developmental defects. However, flies lacking D-p38a are susceptible to some environmental stresses, including heat shock, oxidative stress and starvation. These phenotypes only partially overlap those caused by mutations in D-MEKK1 and dTAK1, suggesting that the D-p38a gene is required to mediate some, but not all, of the functions ascribed to p38 signalling. 相似文献