全文获取类型
收费全文 | 46篇 |
免费 | 0篇 |
专业分类
现状及发展 | 8篇 |
研究方法 | 9篇 |
综合类 | 29篇 |
出版年
2014年 | 1篇 |
2012年 | 2篇 |
2010年 | 1篇 |
2008年 | 1篇 |
2006年 | 3篇 |
2005年 | 3篇 |
2004年 | 1篇 |
2003年 | 1篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1995年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1967年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有46条查询结果,搜索用时 26 毫秒
1.
Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha 总被引:11,自引:0,他引:11
Fruman DA Mauvais-Jarvis F Pollard DA Yballe CM Brazil D Bronson RT Kahn CR Cantley LC 《Nature genetics》2000,26(3):379-382
Phosphoinositide 3-kinases produce 3'-phosphorylated phosphoinositides that act as second messengers to recruit other signalling proteins to the membrane. Pi3ks are activated by many extracellular stimuli and have been implicated in a variety of cellular responses. The Pi3k gene family is complex and the physiological roles of different classes and isoforms are not clear. The gene Pik3r1 encodes three proteins (p85 alpha, p55 alpha and p50 alpha) that serve as regulatory subunits of class IA Pi3ks (ref. 2). Mice lacking only the p85 alpha isoform are viable but display hypoglycaemia and increased insulin sensitivity correlating with upregulation of the p55 alpha and p50 alpha variants. Here we report that loss of all protein products of Pik3r1 results in perinatal lethality. We observed, among other abnormalities, extensive hepatocyte necrosis and chylous ascites. We also noted enlarged skeletal muscle fibres, brown fat necrosis and calcification of cardiac tissue. In liver and muscle, loss of the major regulatory isoform caused a great decrease in expression and activity of class IA Pi3k catalytic subunits; nevertheless, homozygous mice still displayed hypoglycaemia, lower insulin levels and increased glucose tolerance. Our findings reveal that p55 alpha and/or p50 alpha are required for survival, but not for development of hypoglycaemia, in mice lacking p85 alpha. 相似文献
2.
3.
4.
Zusammenfassung 1957 sind vonHajdu et al. Versuche veröffentlicht worden, wonach sich aus verschiedenen Geweben eine Substanz mit Herzglykosid-ähnlicher Wirkung auf Kaltblüterherzen extrahieren lässt, welche als -Palmitoyl-lysolecithin interpretiert wurde. In unseren Versuchen wurde aus Hefe Dipalmitoleyl-lecithin isoliert und daraus durch enzymatische Abspaltung der -ständigen Fettsäure und anschliessende katalytische Hydrierung reines, hämolytisch wirksames -Palmitoyl-lysolecithin hergestellt. Diese Verbindung zeigte jedoch keine den Effekten der Herzglykoside verwandte Wirkung am isolierten Meerschweinchenventrikel sowie an menschlichen Erythrocyten. 相似文献
5.
The use of microring resonators to assist in the evanescent field coupling between dissimilar waveguides is proposed and analyzed. Theoretical analysis based on the coupled mode theory and nu-merical example show that complete cross power transfers can be obtained near the microring resonances. Applications of the device include power dividers, low-power thermo-optic or electro-optic switches, and modulators. 相似文献
6.
Pebay-Peyroula E Dahout-Gonzalez C Kahn R Trézéguet V Lauquin GJ Brandolin G 《Nature》2003,426(6962):39-44
ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved the bovine carrier structure at a resolution of 2.2 A by X-ray crystallography in complex with an inhibitor, carboxyatractyloside. Six alpha-helices form a compact transmembrane domain, which, at the surface towards the space between inner and outer mitochondrial membranes, reveals a deep depression. At its bottom, a hexapeptide carrying the signature of nucleotide carriers (RRRMMM) is located. Our structure, together with earlier biochemical results, suggests that transport substrates bind to the bottom of the cavity and that translocation results from a transient transition from a 'pit' to a 'channel' conformation. 相似文献
7.
8.
Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes 总被引:3,自引:0,他引:3
Yang Q Graham TE Mody N Preitner F Peroni OD Zabolotny JM Kotani K Quadro L Kahn BB 《Nature》2005,436(7049):356-362
In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4(-/-)) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4(-/-) mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes. 相似文献
9.
10.
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. 总被引:107,自引:0,他引:107
Yasuhiko Minokoshi Young-Bum Kim Odile D Peroni Lee G D Fryer Corinna Müller David Carling Barbara B Kahn 《Nature》2002,415(6869):339-343
Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates the oxidation of fatty acids and the uptake of glucose, and prevents the accumulation of lipids in nonadipose tissues, which can lead to functional impairments known as "lipotoxicity". The signalling pathways that mediate the metabolic effects of leptin remain undefined. The 5'-AMP-activated protein kinase (AMPK) potently stimulates fatty-acid oxidation in muscle by inhibiting the activity of acetyl coenzyme A carboxylase (ACC). AMPK is a heterotrimeric enzyme that is conserved from yeast to humans and functions as a 'fuel gauge' to monitor the status of cellular energy. Here we show that leptin selectively stimulates phosphorylation and activation of the alpha2 catalytic subunit of AMPK (alpha2 AMPK) in skeletal muscle, thus establishing a previously unknown signalling pathway for leptin. Early activation of AMPK occurs by leptin acting directly on muscle, whereas later activation depends on leptin functioning through the hypothalamic-sympathetic nervous system axis. In parallel with its activation of AMPK, leptin suppresses the activity of ACC, thereby stimulating the oxidation of fatty acids in muscle. Blocking AMPK activation inhibits the phosphorylation of ACC stimulated by leptin. Our data identify AMPK as a principal mediator of the effects of leptin on fatty-acid metabolism in muscle. 相似文献