全文获取类型
收费全文 | 1159篇 |
免费 | 94篇 |
出版年
2021年 | 20篇 |
2019年 | 8篇 |
2018年 | 12篇 |
2017年 | 11篇 |
2016年 | 21篇 |
2015年 | 23篇 |
2014年 | 29篇 |
2013年 | 33篇 |
2012年 | 55篇 |
2011年 | 51篇 |
2010年 | 24篇 |
2009年 | 30篇 |
2008年 | 55篇 |
2007年 | 47篇 |
2006年 | 34篇 |
2005年 | 49篇 |
2004年 | 47篇 |
2003年 | 41篇 |
2002年 | 37篇 |
2001年 | 30篇 |
2000年 | 39篇 |
1999年 | 36篇 |
1998年 | 13篇 |
1997年 | 17篇 |
1996年 | 16篇 |
1995年 | 9篇 |
1994年 | 13篇 |
1993年 | 10篇 |
1992年 | 30篇 |
1991年 | 17篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 15篇 |
1987年 | 18篇 |
1986年 | 9篇 |
1985年 | 16篇 |
1984年 | 14篇 |
1982年 | 17篇 |
1980年 | 15篇 |
1979年 | 10篇 |
1978年 | 13篇 |
1977年 | 9篇 |
1976年 | 14篇 |
1975年 | 20篇 |
1974年 | 14篇 |
1973年 | 12篇 |
1972年 | 15篇 |
1970年 | 11篇 |
1969年 | 9篇 |
1966年 | 11篇 |
排序方式: 共有1253条查询结果,搜索用时 12 毫秒
111.
Mark R. Herbert Dana L. Siegel Lena Staszewski Charmagne Cayanan Urmi Banerjee Sangeeta Dhamija Jennifer Anderson Amy Fan Li Wang Peter Rix Andrew K. Shiau Tadimeti S. Rao Stewart A. Noble Richard A. Heyman Eric Bischoff Mausumee Guha Ayman Kabakibi Anthony B. Pinkerton 《Bioorganic & medicinal chemistry letters》2010,20(19):5718-5721
Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes. 相似文献
112.
Summary This article proposes saddlepoint approximations to the expectation and variance–covariance function of multitype age‐dependent branching processes. The proposed approximations are found accurate, easy to implement, and much faster to compute than by simulating the process. Multiple applications are presented, including the analyses of clonal data on the generation of oligodendrocytes from their immediate progenitor cells, and on the proliferation of Hela cells. New estimators are also constructed to analyze clonal data. The proposed methods are finally used to approximate the distribution of the generation, which has recently found several applications in cell biology. 相似文献
113.
Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer's disease progression 总被引:1,自引:0,他引:1
Cole AR Noble W van Aalten L Plattner F Meimaridou R Hogan D Taylor M LaFrancois J Gunn-Moore F Verkhratsky A Oddo S LaFerla F Giese KP Dineley KT Duff K Richardson JC Yan SD Hanger DP Allan SM Sutherland C 《Journal of neurochemistry》2007,103(3):1132-1144
Collapsin response mediator protein 2 (CRMP2) is an abundant brain-enriched protein that can regulate microtubule assembly in neurons. This function of CRMP2 is regulated by phosphorylation by glycogen synthase kinase 3 (GSK3) and cyclin-dependent kinase 5 (Cdk5). Here, using novel phosphospecific antibodies, we demonstrate that phosphorylation of CRMP2 at Ser522 (Cdk5-mediated) is increased in Alzheimer's disease (AD) brain, while CRMP2 expression and phosphorylation of the closely related isoform CRMP4 are not altered. In addition, CRMP2 phosphorylation at the Cdk5 and GSK3 sites is increased in cortex and hippocampus of the triple transgenic mouse [presenilin-1 (PS1)(M146V)KI; Thy1.2-amyloid precursor protein (APP)(swe); Thy1.2tau(P301L)] that develops AD-like plaques and tangles, as well as the double (PS1(M146V)KI; Thy1.2-APP(swe)) transgenic mouse. The hyperphosphorylation is similar in magnitude to that in human AD and is evident by 2 months of age, ahead of plaque or tangle formation. Meanwhile, there is no change in CRMP2 phosphorylation in two other transgenic mouse lines that display elevated amyloid beta peptide levels (Tg2576 and APP/amyloid beta-binding alcohol dehydrogenase). Similarly, CRMP2 phosphorylation is normal in hippocampus and cortex of Tau(P301L) mice that develop tangles but not plaques. These observations implicate hyperphosphorylation of CRMP2 as an early event in the development of AD and suggest that it can be induced by a severe APP over-expression and/or processing defect. 相似文献
114.
Microarray experiments typically involve washing steps that remove hybridized nonspecific targets with the purpose of improving the signal-to-noise ratio. The quality of washing ultimately affects downstream analysis of the microarray and interpretation. The paucity of fundamental studies directed towards understanding the dissociation of mixed targets from microarrays makes the development of meaningful washing/dissociation protocols difficult. To fill the void, we examined activation energies and preexponential coefficients of 47 perfect match (PM) and double-mismatch (MM) duplex pairs to discover that there was no statistical difference between the kinetics of the PM and MM duplexes. Based on these findings, we evaluated the nonequilibrium thermal dissociation (NTD) approach, which has been used to identify specific microbial targets in mixed target samples. We found that the major premises for various washing protocols and the NTD approach might be seriously compromised because: (i) nonspecific duplexes do not always dissociate before specific ones, and (ii) the relationship between dissociation rates of the PM and MM duplexes depends on temperature and duplex sequence. Specifically for the NTD, we show that previously suggested use of reference curves, indices of curves and temperature ramps lead to erroneous conclusions. 相似文献
115.
116.
1. Range size, population size and body size, the key macroecological variables, vary temporally both within and across species in response to anthropogenic and natural environmental change. However, resulting temporal trends in the relationships between these variables (i.e. macroecological patterns) have received little attention. 2. Positive relationships between the local abundance and regional occupancy of species (abundance-occupancy relationships) are among the most pervasive of all macroecological patterns. In the absence of formal predictions of how abundance-occupancy relationships may vary temporally, we outline several scenarios of how changes in abundance within species might affect interspecific patterns. 3. We use data on the distribution and abundance of 73 farmland and 55 woodland bird species in Britain over a 32-year period encompassing substantial habitat modification to assess the likelihood of these scenarios. 4. In both farmland and woodland habitats, the interspecific abundance-occupancy relationship changed markedly over the period 1968-99, with a significant decline in the strength of the relationship. 5. Consideration of intraspecific dynamics shows that this has been due to a decoupling of abundance and occupancy particularly in rare and declining species. Insights into the intraspecific processes responsible for the interspecific trend are obtained by analysis of temporal trends in the distribution of individuals between sites, which show patterns consistent with habitat quality declines. 6. This study shows that a profitable approach to ascertaining the nature of human impacts is to link intra- and interspecific processes. In the case of British farmland and woodland birds, changes to the environment lead to species-specific responses in large-scale distributions. These species-specific changes are the driver of the observed changes in the form and strength of the interspecific relationship. 相似文献
117.
Thorp DB Haist JV Leppard J Milne KJ Karmazyn M Noble EG 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(1):R363-R371
Acute exercise increases myocardial tolerance to ischemia-reperfusion (I-R) injury in male but not in female rat hearts, possibly due to a decreased heat shock protein 70 (Hsp70) response in the female hearts. This study examined whether repetitive exercise training would increase Hsp70 and myocardial tolerance to I-R injury in female rat hearts. Adaptations in myocardial manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) were also assessed. Ten-week old male (M) and female (F) Sprague-Dawley rats (n = 40 total) exercise-trained for 14 wk; the last 8 wk consisted of running 1 h at 30 m/min (2% incline), 5 days/wk. Following training, left ventricle mechanical function (LVMF) was monitored for 30 min of reperfusion following 30 min of global ischemia (Langendorff procedure). Myocardial Hsp70 content was not different in M and F control groups, while increases were observed in both trained groups (M greater than F; P < 0.05). Although MnSOD content did not differ between groups, endothelial nitric oxide synthase (eNOS) levels were decreased in F, with no change in M, following training (P < 0.05). Hearts from control F demonstrated a greater recuperation of all indices of LVMF following I-R compared with control M hearts (P < 0.05). Hearts of trained M exhibited improved recovery of LVMF (left ventricular diastolic pressure, left ventricular end-diastolic pressure, +dP/dt, -dP/dt) during reperfusion compared with control M hearts (P < 0.05). In contrast, hearts of trained F did not show any change in recovery from I-R. Hence, exercise training is more beneficial to M than F in improving myocardial function following I-R injury. 相似文献
118.
MOTIVATION: This work aims to develop computational methods to annotate protein structures in an automated fashion. We employ a support vector machine (SVM) classifier to map from a given class of structures to their corresponding structural (SCOP) or functional (Gene Ontology) annotation. In particular, we build upon recent work describing various kernels for protein structures, where a kernel is a similarity function that the classifier uses to compare pairs of structures. RESULTS: We describe a kernel that is derived in a straightforward fashion from an existing structural alignment program, MAMMOTH. We find in our benchmark experiments that this kernel significantly out-performs a variety of other kernels, including several previously described kernels. Furthermore, in both benchmarks, classifying structures using MAMMOTH alone does not work as well as using an SVM with the MAMMOTH kernel. AVAILABILITY: http://noble.gs.washington.edu/proj/3dkernel 相似文献
119.
120.