全文获取类型
收费全文 | 7404篇 |
免费 | 983篇 |
国内免费 | 1篇 |
出版年
2021年 | 86篇 |
2019年 | 65篇 |
2018年 | 80篇 |
2017年 | 76篇 |
2016年 | 111篇 |
2015年 | 186篇 |
2014年 | 202篇 |
2013年 | 272篇 |
2012年 | 322篇 |
2011年 | 327篇 |
2010年 | 238篇 |
2009年 | 179篇 |
2008年 | 315篇 |
2007年 | 265篇 |
2006年 | 275篇 |
2005年 | 225篇 |
2004年 | 252篇 |
2003年 | 250篇 |
2002年 | 221篇 |
2001年 | 218篇 |
2000年 | 207篇 |
1999年 | 176篇 |
1998年 | 119篇 |
1997年 | 100篇 |
1996年 | 100篇 |
1995年 | 100篇 |
1994年 | 92篇 |
1993年 | 90篇 |
1992年 | 142篇 |
1991年 | 182篇 |
1990年 | 196篇 |
1989年 | 139篇 |
1988年 | 149篇 |
1987年 | 153篇 |
1986年 | 143篇 |
1985年 | 133篇 |
1984年 | 117篇 |
1983年 | 104篇 |
1982年 | 95篇 |
1981年 | 100篇 |
1980年 | 98篇 |
1979年 | 111篇 |
1978年 | 102篇 |
1977年 | 87篇 |
1976年 | 72篇 |
1975年 | 69篇 |
1974年 | 96篇 |
1973年 | 95篇 |
1972年 | 82篇 |
1971年 | 79篇 |
排序方式: 共有8388条查询结果,搜索用时 15 毫秒
11.
Shreaya Chakroborty Clark Briggs Megan B. Miller Ivan Goussakov Corinne Schneider Joyce Kim Jaime Wicks Jill C. Richardson Vincent Conklin Benjamin G. Cameransi Grace E. Stutzmann 《PloS one》2012,7(12)
Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca2+ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca2+ signaling, predominantly through the ER-localized inositol triphosphate (IP3) and ryanodine receptors (RyR). In particular, the RyR-mediated Ca2+ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic) AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks) with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca2+ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca2+ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca2+ aberrations in AD, and propose a novel strategy to preserve synaptic function, and thereby cognitive function, in early AD patients. 相似文献
12.
13.
14.
15.
David Clark 《BMJ (Clinical research ed.)》2002,324(7342):905-907
16.
17.
Two simulations of plankton dynamics are combined: an N/P/Zmodel and an optimal foraging strategy dependent on variablevertical migration. We show that there is no optimal individualstrategy consistent with a copepod population that has two generationsand is a significant grazer on its limiting food supply. Alternativeroles for did vertical migration are considered. 相似文献
18.
19.
20.