全文获取类型
收费全文 | 233篇 |
免费 | 49篇 |
出版年
2019年 | 4篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 5篇 |
2011年 | 14篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 11篇 |
2007年 | 4篇 |
2006年 | 5篇 |
2005年 | 2篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1995年 | 3篇 |
1992年 | 4篇 |
1991年 | 6篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 9篇 |
1974年 | 5篇 |
1973年 | 7篇 |
1972年 | 6篇 |
1970年 | 2篇 |
1965年 | 2篇 |
1915年 | 2篇 |
1914年 | 2篇 |
1911年 | 2篇 |
1901年 | 2篇 |
1897年 | 4篇 |
排序方式: 共有282条查询结果,搜索用时 109 毫秒
21.
R. T. Michell 《BMJ (Clinical research ed.)》1897,1(1896):1104-1106
22.
23.
Xiao L. Moore Danielle Michell Sabrina Lee Michael R. Skilton Rajesh Nair John B. Dixon Anthony M. Dart Jaye Chin-Dusting 《PloS one》2013,8(1)
Carotid intima-media-thickness (cIMT) and carotid distensibility (distensibility), structural and functional properties of carotid arteries respectively, are early markers, as well as strong predictors of cardiovascular disease (CVD). The characteristic of these two parameters in individuals with BMI>40.0 kg/m2 (Class III obesity), however, are largely unknown. The present study was designed to document cIMT and distensibility in this population and to relate these to other factors with established association with CVD in obesity. The study included 96 subjects (65 with BMI>40.0 kg/m2 and 31, age- and gender-matched, with BMI of 18.5 to 30.0 kg/m2). cIMT and distensibility were measured by non-invasive high resolution ultrasonography, circulatory CD133+/KDR+ angiogenic cells and endothelial microparticles (EMP) by flow cytometry, and plasma levels of adipokines, growth factors and cytokines by Luminex immunoassay kits. The study results demonstrated increased cIMT (0.62±0.11 mm vs. 0.54±0.08 mm, P = 0.0002) and reduced distensibility (22.52±10.79 10−3kpa−1
vs. 29.91±12.37 10−3kpa−1, P<0.05) in individuals with BMI>40.0 kg/m2. Both cIMT and distensibility were significantly associated with traditional CVD risk factors, adiposity/adipokines and inflammatory markers but had no association with circulating angiogenic cells. We also demonstrated, for the first time, elevated plasma EMP levels in individuals with BMI>40.0 kg/m2. In conclusion, cIMT is increased and distensibility reduced in Class III obesity with the changes predominantly related to conventional CVD risk factors present in this condition, demonstrating that both cIMT and distensibility remain as CVD markers in Class III obesity. 相似文献
24.
Robert Lehmann Damien J. Lightfoot Celia Schunter Craig T. Michell Hajime Ohyanagi Katsuhiko Mineta Sylvain Foret Michael L. Berumen David J. Miller Manuel Aranda Takashi Gojobori Philip L. Munday Timothy Ravasi 《Molecular ecology resources》2019,19(3):570-585
The iconic orange clownfish, Amphiprion percula, is a model organism for studying the ecology and evolution of reef fishes, including patterns of population connectivity, sex change, social organization, habitat selection and adaptation to climate change. Notably, the orange clownfish is the only reef fish for which a complete larval dispersal kernel has been established and was the first fish species for which it was demonstrated that antipredator responses of reef fishes could be impaired by ocean acidification. Despite its importance, molecular resources for this species remain scarce and until now it lacked a reference genome assembly. Here, we present a de novo chromosome‐scale assembly of the genome of the orange clownfish Amphiprion percula. We utilized single‐molecule real‐time sequencing technology from Pacific Biosciences to produce an initial polished assembly comprised of 1,414 contigs, with a contig N50 length of 1.86 Mb. Using Hi‐C‐based chromatin contact maps, 98% of the genome assembly were placed into 24 chromosomes, resulting in a final assembly of 908.8 Mb in length with contig and scaffold N50s of 3.12 and 38.4 Mb, respectively. This makes it one of the most contiguous and complete fish genome assemblies currently available. The genome was annotated with 26,597 protein‐coding genes and contains 96% of the core set of conserved actinopterygian orthologs. The availability of this reference genome assembly as a community resource will further strengthen the role of the orange clownfish as a model species for research on the ecology and evolution of reef fishes. 相似文献
25.
Cellular stress regulates the nucleocytoplasmic distribution of the protein-tyrosine phosphatase TCPTP 总被引:5,自引:0,他引:5
Lam MH Michell BJ Fodero-Tavoletti MT Kemp BE Tonks NK Tiganis T 《The Journal of biological chemistry》2001,276(40):37700-37707
Specific cellular stresses, including hyperosmotic stress, caused a dramatic but reversible cytoplasmic accumulation of the otherwise nuclear 45-kDa variant of the protein-tyrosine phosphatase TCPTP (TC45). In the cytoplasm, TC45 dephosphorylated the epidermal growth factor receptor and down-regulated the hyperosmotic stress-induced activation of the c-Jun N-terminal kinase. The hyperosmotic stress-induced nuclear exit of TC45 was not inhibited by leptomycin B, indicating that TC45 nuclear exit was independent of the exportin CRM-1. Moreover, hyperosmotic stress did not induce the cytoplasmic accumulation of a green fluorescent protein-TC45 fusion protein that was too large to diffuse across the nuclear pore. Our results indicate that TC45 nuclear exit may occur by passive diffusion and that cellular stress may induce the cytoplasmic accumulation of TC45 by inhibiting nuclear import. Neither p42(Erk2) nor the stress-activated c-Jun N-terminal kinase or p38 mediated the stress-induced redistribution of TC45. We found that only those stresses that stimulated the metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) induced the redistribution of TC45. In addition, specific pharmacological activation of the AMPK was sufficient to cause the accumulation of TC45 in the cytoplasm. Our studies indicate that specific stress-activated signaling pathways that involve the AMPK can alter the nucleocytoplasmic distribution of TC45 and thus regulate TC45 function in vivo. 相似文献
26.
Reciprocal phosphorylation and regulation of endothelial nitric-oxide synthase in response to bradykinin stimulation 总被引:13,自引:0,他引:13
Harris MB Ju H Venema VJ Liang H Zou R Michell BJ Chen ZP Kemp BE Venema RC 《The Journal of biological chemistry》2001,276(19):16587-16591
Endothelial nitric-oxide synthase (eNOS) is phosphorylated at Ser-1179 (bovine sequence) by Akt after growth factor or shear stress stimulation of endothelial cells, resulting in increased eNOS activity. Purified eNOS is also phosphorylated at Thr-497 by purified AMP-activated protein kinase, resulting in decreased eNOS activity. We investigated whether bradykinin (BK) stimulation of bovine aortic endothelial cells (BAECs) regulates eNOS through Akt activation and Ser-1179 or Thr-497 phosphorylation. Akt is transiently activated in BK-stimulated BAECs. Activation is blocked completely by wortmannin and LY294002, inhibitors of phosphatidylinositol 3-kinase, suggesting that Akt activation occurs downstream from phosphatidylinositol 3-kinase. BK stimulates a transient phosphorylation of eNOS at Ser-1179 that is correlated temporally with a transient dephosphorylation of eNOS at Thr-497. Phosphorylation at Ser-1179, but not dephosphorylation at Thr-497, is blocked by wortmannin and LY294002. BK also stimulates a transient nitric oxide (NO) release from BAECs with a time-course similar to Ser-1179 phosphorylation and Thr-497 dephosphorylation. NO release is not altered by wortmannin. BK-stimulated dephosphorylation of Thr-497 and NO release are blocked by the calcineurin inhibitor, cyclosporin A. These data suggest that BK activation of eNOS in BAECs primarily involves deinhibition of the enzyme through calcineurin-mediated dephosphorylation at Thr-497. 相似文献
27.
Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase 总被引:16,自引:0,他引:16
Michell BJ Chen Zp Tiganis T Stapleton D Katsis F Power DA Sim AT Kemp BE 《The Journal of biological chemistry》2001,276(21):17625-17628
Endothelial nitric-oxide synthase (eNOS) is an important regulatory enzyme in the cardiovascular system catalyzing the production of NO from arginine. Multiple protein kinases including Akt/PKB, cAMP-dependent protein kinase (PKA), and the AMP-activated protein kinase (AMPK) activate eNOS by phosphorylating Ser-1177 in response to various stimuli. During VEGF signaling in endothelial cells, there is a transient increase in Ser-1177 phosphorylation coupled with a decrease in Thr-495 phosphorylation that reverses over 10 min. PKC signaling in endothelial cells inhibits eNOS activity by phosphorylating Thr-495 and dephosphorylating Ser-1177 whereas PKA signaling acts in reverse by increasing phosphorylation of Ser-1177 and dephosphorylation of Thr-495 to activate eNOS. Both phosphatases PP1 and PP2A are associated with eNOS. PP1 is responsible for dephosphorylation of Thr-495 based on its specificity for this site in both eNOS and the corresponding synthetic phosphopeptide whereas PP2A is responsible for dephosphorylation of Ser-1177. Treatment of endothelial cells with calyculin selectively blocks PKA-mediated dephosphorylation of Thr-495 whereas okadaic acid selectively blocks PKC-mediated dephosphorylation of Ser-1177. These results show that regulation of eNOS activity involves coordinated signaling through Ser-1177 and Thr-495 by multiple protein kinases and phosphatases. 相似文献
28.
AMPK beta subunit targets metabolic stress sensing to glycogen 总被引:12,自引:0,他引:12
Polekhina G Gupta A Michell BJ van Denderen B Murthy S Feil SC Jennings IG Campbell DJ Witters LA Parker MW Kemp BE Stapleton D 《Current biology : CB》2003,13(10):867-871
AMP-activated protein kinase (AMPK) is a multisubstrate enzyme activated by increases in AMP during metabolic stress caused by exercise, hypoxia, lack of cell nutrients, as well as hormones, including adiponectin and leptin. Furthermore, metformin and rosiglitazone, frontline drugs used for the treatment of type II diabetes, activate AMPK. Mammalian AMPK is an alphabetagamma heterotrimer with multiple isoforms of each subunit comprising alpha1, alpha2, beta1, beta2, gamma1, gamma2, and gamma3, which have varying tissue and subcellular expression. Mutations in the AMPK gamma subunit cause glycogen storage disease in humans, but the molecular relationship between glycogen and the AMPK/Snf1p kinase subfamily has not been apparent. We show that the AMPK beta subunit contains a functional glycogen binding domain (beta-GBD) that is most closely related to isoamylase domains found in glycogen and starch branching enzymes. Mutation of key glycogen binding residues, predicted by molecular modeling, completely abolished beta-GBD binding to glycogen. AMPK binds to glycogen but retains full activity. Overexpressed AMPK beta1 localized to specific mammalian subcellular structures that corresponded with the expression pattern of glycogen phosphorylase. Glycogen binding provides an architectural link between AMPK and a major cellular energy store and juxtaposes AMPK to glycogen bound phosphatases. 相似文献
29.
Industrial microbiology of solar salt production 总被引:3,自引:0,他引:3
Javor BJ 《Journal of industrial microbiology & biotechnology》2002,28(1):42-47
Solar salterns can be modeled as giant outdoor chemostats, much like a series of dams on a slow-moving river. Microorganisms
and their products play an essential, but sometimes uncharacterized, role in salt production in these ponds, from seawater
salinity up through NaCl saturation. They may physically affect the evaporation process and their by-products may chemically
modify or bind with dissolved ions. Many solar salt facilities engage microbiologists to establish monitoring programs for
analyses of nutrients, standing crop and associated biological variables in the ponds. Other solar salt companies engage microbiologists
only when there are “crises” in the ponds that interfere with salt production. Journal of Industrial Microbiology & Biotechnology (2002) 28, 42–47 DOI: 10.1038/sj/jim/7000173
Received 20 May 2001/ Accepted in revised form 13 June 2001 相似文献
30.