全文获取类型
收费全文 | 173篇 |
免费 | 13篇 |
国内免费 | 6篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 4篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 7篇 |
2013年 | 13篇 |
2012年 | 11篇 |
2011年 | 22篇 |
2010年 | 9篇 |
2009年 | 13篇 |
2008年 | 8篇 |
2007年 | 10篇 |
2006年 | 10篇 |
2005年 | 8篇 |
2004年 | 10篇 |
2003年 | 3篇 |
2002年 | 7篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1978年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有192条查询结果,搜索用时 0 毫秒
191.
192.
Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. 总被引:3,自引:0,他引:3
H Senzaki C J Smith G J Juang T Isoda S P Mayer A Ohler N Paolocci G F Tomaselli J M Hare D A Kass 《FASEB journal》2001,15(10):1718-1726
Recent studies implicate increased cGMP synthesis as a postreceptor contributor to reduced cardiac sympathetic responsiveness. Here we provide the first evidence that modulation of this interaction by cGMP-specific phosphodiesterase PDE5A is also diminished in failing hearts, providing a novel mechanism for blunted beta-adrenergic signaling in this disorder. In normal conscious dogs chronically instrumented for left ventricular pressure-dimension analysis, PDE5A inhibition by EMD82639 had modest basal effects but markedly blunted dobutamine-enhanced systolic and diastolic function. In failing hearts (tachypacing model), however, EMD82639 had negligible effects on either basal or dobutamine-stimulated function. Whole myocardium from failing hearts had 50% lower PDE5A protein expression and 30% less total and EMD92639-inhibitable cGMP-PDE activity. Although corresponding myocyte protein and enzyme activity was similar among groups, the proportion of EMD82639-inhibitable activity was significantly lower in failure cells. Immunohistochemistry confirmed PDE5A expression in both the vasculature and myocytes of normal and failing hearts, but there was loss of z-band localization in failing myocytes that suggested altered intracellular localization. Thus, PDE5A regulation of cGMP in the heart can potently modulate beta-adrenergic stimulation, and alterations in enzyme localization and reduced synthesis may blunt this pathway in cardiac failure, contributing to dampening of the beta-adrenergic response. 相似文献