全文获取类型
收费全文 | 548篇 |
免费 | 32篇 |
国内免费 | 2篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 14篇 |
2020年 | 1篇 |
2019年 | 6篇 |
2018年 | 12篇 |
2017年 | 7篇 |
2016年 | 12篇 |
2015年 | 20篇 |
2014年 | 16篇 |
2013年 | 33篇 |
2012年 | 53篇 |
2011年 | 46篇 |
2010年 | 24篇 |
2009年 | 22篇 |
2008年 | 45篇 |
2007年 | 35篇 |
2006年 | 38篇 |
2005年 | 36篇 |
2004年 | 24篇 |
2003年 | 28篇 |
2002年 | 29篇 |
2001年 | 12篇 |
2000年 | 7篇 |
1999年 | 3篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有582条查询结果,搜索用时 671 毫秒
91.
MOTIVATION: High-throughput 'ChIP-chip' and 'ChIP-seq' methodologies generate sufficiently large data sets that analysis poses significant informatics challenges, particularly for research groups with modest computational support. To address this challenge, we devised a software platform for storing, analyzing and visualizing high resolution genome-wide binding data. GeneTrack automates several steps of a typical data processing pipeline, including smoothing and peak detection, and facilitates dissemination of the results via the web. Our software is freely available via the Google Project Hosting environment at http://genetrack.googlecode.com 相似文献
92.
The opioid receptor system in the central nervous system controls a number of physiological processes, most notably pain. However, most opioids currently available have a variety of side-effects as well as exhibiting tolerance. Tolerance is most likely to be a complex phenomenon, however, the role of receptor internalisation is thought to play a crucial role. In this study, we examined the role of aromaticity in ligand-mediated receptor internalisation of the mu-opioid receptor (MOPR). These studies show that the amount of receptor internalisation may be dependant on the amphiphilicity of the ligand. Specifically, deletion of the C-terminus aromatic residues of endomorphin 1, particularly tryptophan reduces receptor-mediated internalisation whilst the addition of tryptophan within the enkephalin sequence increases receptor internalisation and decreases tolerance. 相似文献
93.
Fujita Y Abdel-Aal AB Wimmer N Batzloff MR Good MF Toth I 《Bioorganic & medicinal chemistry》2008,16(19):8907-8913
Synthesis of four glycolipids with different number of lauroyl groups on glucose or cellobiose as scaffolds is described. Their immunological evaluations either admixed with or covalently linked to J8, a peptide antigen derived from the C-terminus of the antiphagocytic M-protein of group A streptococcus, are also investigated. Administration of mixtures of J8 and glycolipids to B10BR (H-2(k)) mice induced low-levels of J8-specific IgG antibodies. While glycolipopeptides, in which J8 was covalently linked to the synthetic glycolipids, demonstrated high-levels of antibody titers comparable with the co-administration of these glycolipopeptides with complete Freund's adjuvant, suggesting clearly the strong potency of the synthesized glycolipids as self-adjuvanting moieties. 相似文献
94.
Christian Cortés-Rojo Elizabeth Calderón-Cortés Mónica Clemente-Guerrero Mirella Estrada-Villagómez Salvador Manzo-Avalos Ricardo Mejía-Zepeda Istvan Boldogh Alfredo Saavedra-Molina 《Journal of bioenergetics and biomembranes》2009,41(1):15-28
Lipoperoxidative damage to the respiratory chain proteins may account for disruption in mitochondrial electron transport chain
(ETC) function and could lead to an augment in the production of reactive oxygen species (ROS). To test this hypothesis, we
investigated the effects of lipoperoxidation on ETC function and cytochromes spectra of Saccharomyces cerevisiae mitochondria. We compared the effects of Fe2+ treatment on mitochondria isolated from yeast with native (lipoperoxidation-resistant) and modified (lipoperoxidation-sensitive)
fatty acid composition. Augmented sensitivity to oxidative stress was observed in the complex III-complex IV segment of the
ETC. Lipoperoxidation did not alter the cytochromes content. Under lipoperoxidative conditions, cytochrome c reduction by succinate was almost totally eliminated by superoxide dismutase and stigmatellin. Our results suggest that lipoperoxidation
impairs electron transfer mainly at cytochrome b in complex III, which leads to increased resistance to antimycin A and ROS generation due to an electron leak at the level
of the QO site of complex III. 相似文献
95.
96.
Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein 总被引:1,自引:0,他引:1
Gurusamy N Lekli I Gorbunov NV Gherghiceanu M Popescu LM Das DK 《Journal of cellular and molecular medicine》2009,13(2):373-387
Autophagy is an intracellular process in which a cell digests its own constituents via lysosomal degradative pathway. Though autophagy has been shown in several cardiac diseases like heart failure, hypertrophy and ischaemic cardiomyopathy, the role and the regulation of autophagy is still largely unknown. Bcl-2-associated athanogene (BAG-1) is a multifunctional pro-survival molecule that binds with Hsp70/Hsc70. In this study, myocardial adaptation to ischaemia by repeated brief episodes of ischaemia and reperfusion (I/R) prior to lethal I/R enhanced the expression of autophagosomal membrane specific protein light chain 3 (LC3)-II, and Beclin-1, a molecule involved in autophagy and BAG-1. Autophagosomes structures were found in the adapted myocardium through electron microscopy. Co-immunoprecipitation and co-immunofluorescence analyses revealed that LC3-II was bound with BAG-1. Inhibition of autophagy by treating rats with Wortmannin (15 μg/kg; intraperitoneally) abolished the ischaemic adaptation-induced induction of LC3-II, Beclin-1, BAG-1 and cardioprotection. Intramyocardial injection of BAG-1 siRNA attenuated the induction of LC3-II, and abolished the cardioprotection achieved by adaptation. Furthermore, hypoxic adaptation in cardiac myoblast cells induced LC3-II and BAG-1. BAG-1 siRNA treatment attenuated hypoxic adaptation-induced LC3-II and BAG-1, and abolished improvement in cardiac cell survival and reduction of cell death. These results clearly indicate that myocardial protection elicited by adaptation is mediated at least in part via up-regulation of autophagy in association with BAG-1 protein. 相似文献
97.
Nilesh Dharajiya Swapnil Vaidya Mala Sinha Bruce Luxon Istvan Boldogh Sanjiv Sur 《PloS one》2009,4(12)
According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE) using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1), Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1) Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2) Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation. 相似文献
98.
Szatmari I Vámosi G Brazda P Balint BL Benko S Széles L Jeney V Ozvegy-Laczka C Szántó A Barta E Balla J Sarkadi B Nagy L 《The Journal of biological chemistry》2006,281(33):23812-23823
99.
100.
Presence of Anti-Microbial Antibodies in Liver Cirrhosis – A Tell-Tale Sign of Compromised Immunity?
Papp M Norman GL Vitalis Z Tornai I Altorjay I Foldi I Udvardy M Shums Z Dinya T Orosz P Lombay B Par G Par A Veres G Csak T Osztovits J Szalay F Lakatos PL 《PloS one》2010,5(9):e12957