全文获取类型
收费全文 | 508916篇 |
免费 | 167819篇 |
国内免费 | 27572篇 |
出版年
2018年 | 5682篇 |
2016年 | 7065篇 |
2015年 | 9999篇 |
2014年 | 11040篇 |
2013年 | 14490篇 |
2012年 | 16637篇 |
2011年 | 17132篇 |
2010年 | 13602篇 |
2009年 | 17535篇 |
2008年 | 15946篇 |
2007年 | 16339篇 |
2006年 | 14627篇 |
2005年 | 14426篇 |
2004年 | 14295篇 |
2003年 | 13259篇 |
2002年 | 13858篇 |
2001年 | 22691篇 |
2000年 | 21019篇 |
1999年 | 21312篇 |
1998年 | 13131篇 |
1997年 | 12958篇 |
1996年 | 12111篇 |
1995年 | 12409篇 |
1994年 | 11737篇 |
1993年 | 11431篇 |
1992年 | 18896篇 |
1991年 | 18362篇 |
1990年 | 18653篇 |
1989年 | 17723篇 |
1988年 | 16557篇 |
1987年 | 15322篇 |
1986年 | 14410篇 |
1985年 | 14087篇 |
1984年 | 11546篇 |
1983年 | 9709篇 |
1982年 | 8679篇 |
1981年 | 7991篇 |
1980年 | 7468篇 |
1979年 | 10515篇 |
1978年 | 8836篇 |
1977年 | 8259篇 |
1976年 | 7765篇 |
1975年 | 8052篇 |
1974年 | 8924篇 |
1973年 | 8840篇 |
1972年 | 8567篇 |
1971年 | 7826篇 |
1970年 | 6853篇 |
1969年 | 6839篇 |
1968年 | 6086篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
1.
Laura C. Burzynski Melanie Humphry Martin R. Bennett Murray C. H. Clarke 《The Journal of biological chemistry》2015,290(41):25188-25196
Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection. 相似文献
2.
Sven Hoefman David van der Ha Nico Boon Peter Vandamme Paul De Vos Kim Heylen 《Antonie van Leeuwenhoek》2014,105(2):353-366
The growth of twelve methanotrophic strains within the genus Methylomonas, including the type strains of Methylomonas methanica and Methylomonas koyamae, was evaluated with 40 different variations of standard diluted nitrate mineral salts medium in 96-well microtiter plates. Unique profiles of growth preference were observed for each strain, showing a strong strain dependency for optimal growth conditions, especially with regards to the preferred concentration and nature of the nitrogen source. Based on the miniaturized screening results, a customized medium was designed for each strain, allowing the improvement of the growth of several strains in a batch setup, either by a reduction of the lag phase or by faster biomass accumulation. As such, the maintenance of fastidious strains could be facilitated while the growth of fast-growing Methylomonas strains could be further improved. Methylomonas sp. R-45378 displayed a 50 % increase in cell dry weight when grown in its customized medium and showed the lowest observed nitrogen and oxygen requirement of all tested strains. We demonstrate that the presented miniaturized approach for medium optimization is a simple tool allowing the quick generation of strain-specific growth preference data that can be applied downstream of an isolation campaign. This approach can also be applied as a first step in the search for strains with biotechnological potential, to facilitate cultivation of fastidious strains or to steer future isolation campaigns. 相似文献
3.
4.
5.
6.
According to the ideomotor theory, actions are represented in terms of their perceptual effects, offering a solution for the correspondence problem of imitation (how to translate the observed action into a corresponding motor output). This effect-based coding of action is assumed to be acquired through action-effect learning. Accordingly, performing an action leads to the integration of the perceptual codes of the action effects with the motor commands that brought them about. While ideomotor theory is invoked to account for imitation, the influence of action-effect learning on imitative behavior remains unexplored. In two experiments, imitative performance was measured in a reaction time task following a phase of action-effect acquisition. During action-effect acquisition, participants freely executed a finger movement (index or little finger lifting), and then observed a similar (compatible learning) or a different (incompatible learning) movement. In Experiment 1, finger movements of left and right hands were presented as action-effects during acquisition. In Experiment 2, only right-hand finger movements were presented during action-effect acquisition and in the imitation task the observed hands were oriented orthogonally to participants’ hands in order to avoid spatial congruency effects. Experiments 1 and 2 showed that imitative performance was improved after compatible learning, compared to incompatible learning. In Experiment 2, although action-effect learning involved perception of finger movements of right hand only, imitative capabilities of right- and left-hand finger movements were equally affected. These results indicate that an observed movement stimulus processed as the effect of an action can later prime execution of that action, confirming the ideomotor approach to imitation. We further discuss these findings in relation to previous studies of action-effect learning and in the framework of current ideomotor approaches to imitation. 相似文献
7.
Thomas Arn Hansen Helena Fridholm Tobias Guldberg Fr?slev Kristín Rós Kjartansdóttir Eske Willerslev Lars Peter Nielsen Anders Johannes Hansen 《PloS one》2015,10(11)
Rattus norvegicus (R. norvegicus) are ubiquitous and their presence has several effects on the human populations in our urban areas on a global scale. Both historically and presently, this close interaction has facilitated the dissemination of many pathogens to humans, making screening for potentially zoonotic and emerging viruses in rats highly relevant. We have investigated faecal samples from R. norvegicus collected from urban areas using a protocol based on metagenomic enrichment of circular DNA genomes and subsequent sequencing. We found a new type of papillomavirus, with a L1 region 82% identical to that of the known R. norvegicus Papillomavirus 2. Additionally, we found 20 different circular replication associated protein (Rep)-encoding single stranded DNA (CRESS-DNA) virus-like genomes, one of which has homology to the replication-associated gene of Beak and feather disease virus. Papillomaviruses are a group of viruses known for their carcinogenic potential, and although they are known to infect several different vertebrates, they are mainly studied and characterised in humans. CRESS-DNA viruses are found in many different environments and tissue types. Both papillomaviruses and CRESS-DNA viruses are known to have pathogenic potential and screening for novel and known viruses in R. norvegicus could help identify viruses with pathogenic potential. 相似文献
8.
9.
H. James Spooner 《CMAJ》1996,154(12):1875-1876
10.
Imaging in five dimensions: time-dependent membrane potentials in individual mitochondria. 总被引:13,自引:2,他引:11
Because of its importance in the chemiosmotic theory, mitochondrial membrane potential has been the object of many investigations. Significantly, however, quantitative data on how energy transduction might be regulated or perturbed by the physiological state of the cell has only been gathered via indirect studies on isolated mitochondrial suspensions; quantitative studies on individual mitochondria in situ have not been possible because of their small size, their intrinsic motility, and the absence of appropriate analytical reagents. In this article, we combine techniques for rapid, high resolution, quantitative three-dimensional imaging microscopy and mathematical modeling to determine accurate distributions of a potentiometric fluorescent probe between the cytosol and individual mitochondria inside a living cell. Analysis of this distribution via the Nernst equation permits assignment of potentials to each of the imaged mitochondrial membranes. The mitochondrial membrane potentials are distributed over a narrow range centered at -150 mV within the neurites of differentiated neuroblastoma cells. We find that the membrane potential of a single mitochondrion is generally remarkably stable over times of 40-80 s, but significant fluctuations can occasionally be seen. The motility of individual mitochondria is not directly correlated to membrane potential, but mitochondria do become immobile after prolonged treatment with respiratory inhibitors or uncouplers. Thus, three spatial dimensions, a key physiological parameter, and their changes over time are all quantitated for objects at the resolution limit of light microscopy. The methods described may be readily extended to permit investigations of how mitochondrial function is integrated with other processes in the intact cell. 相似文献