首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   968篇
  免费   73篇
  2023年   4篇
  2022年   6篇
  2021年   28篇
  2020年   10篇
  2019年   18篇
  2018年   11篇
  2017年   15篇
  2016年   28篇
  2015年   43篇
  2014年   55篇
  2013年   53篇
  2012年   60篇
  2011年   89篇
  2010年   54篇
  2009年   39篇
  2008年   61篇
  2007年   73篇
  2006年   68篇
  2005年   49篇
  2004年   44篇
  2003年   49篇
  2002年   49篇
  2001年   10篇
  2000年   4篇
  1999年   13篇
  1998年   5篇
  1997年   9篇
  1996年   4篇
  1995年   8篇
  1994年   8篇
  1993年   8篇
  1992年   3篇
  1991年   8篇
  1990年   5篇
  1989年   3篇
  1988年   4篇
  1987年   3篇
  1986年   4篇
  1985年   6篇
  1984年   4篇
  1983年   2篇
  1982年   2篇
  1981年   2篇
  1980年   3篇
  1979年   4篇
  1975年   2篇
  1973年   2篇
  1968年   1篇
  1967年   1篇
  1960年   1篇
排序方式: 共有1041条查询结果,搜索用时 15 毫秒
41.
Sterility virulence, or the reduction in host fecundity due to infection, occurs in many host–pathogen systems. Notably, sterility virulence is more common for sexually transmitted infections (STIs) than for directly transmitted pathogens, while other forms of virulence tend to be limited in STIs. This has led to the suggestion that sterility virulence may have an adaptive explanation. By focusing upon finite population models, we show that the observed patterns of sterility virulence can be explained by consideration of the epidemiological differences between STIs and directly transmitted pathogens. In particular, when pathogen transmission is predominantly density invariant (as for STIs), and mortality is density dependent, sterility virulence can be favored by demographic stochasticity, whereas if pathogen transmission is predominantly density dependent, as is common for most directly transmitted pathogens, sterility virulence is disfavored. We show these conclusions can hold even if there is a weak selective advantage to sterilizing.  相似文献   
42.
A 3‐year study (2014–2016) was conducted at Rocky Harbour near the west coast of Newfoundland, Canada, to record the abundance and phenology of adult spruce budworms captured at traps, using a factorial design (light traps and pheromone traps deployed contiguously or segregated spatially). Budworms were most abundant and occurred seasonally earlier in 2014 than in 2015 and 2016; these findings held generally true for males and females. The geographic setting of Newfoundland (large island isolated from the mainland by an oceanic barrier of >100 km across) provides an ideal location to discriminate local flight from long‐range immigrations; in our study, however, immigrations cannot be ruled out for any single day of trapping due to broad overlap in emergence patterns at Rocky Harbour relative to forest stands with known populations of budworms on the mainland. Based on moderate daily variation in adult abundance, however, major immigration events (defined as external deposition of budworms with large numerical amplitude) likely did not take place at Rocky Harbor between 2014 and 2016. Males were more abundant at light traps coupled with pheromone traps, whereas abundance of males at pheromone traps was similar with or without contiguous light traps. This outcome may be mediated by lower range of attraction for light traps (usually <100 m) and (generally assumed to be several hundreds of meters). Females were equally abundant at light traps with or without pheromone traps. As expected, males were captured earlier in the season at pheromone traps than at light traps, and females occurred later in the season due to protandry. The onset of flight observed at light traps or pheromone traps in 2015 and 2016 occurred 10–15 days later than simulated predictions; caution is thus warranted as to conclusions derived on computer modeling of adult emergence.  相似文献   
43.
Benign and malignant pulmonary tumors have been reported in both Old World and New World monkeys but are uncommon. Hemangiomas are also rarely reported in nonhuman primates. Here we present a case of two primary neoplasms (a papillary adenocarcinoma of bronchioloalveolar origin and multiple cavernous subcutaneous hemangiomas) arising in an aged squirrel monkey (Saimiri sciureus).  相似文献   
44.
45.
beta-Amyloid (A beta) has been strongly implicated in the pathophysiology of Alzheimer's disease (AD), but the means by which the aggregated form of this molecule induces neuronal death have not been fully defined. Here, we examine the role of the c-Jun N-terminal kinases (JNKs) and of their substrate, c-Jun, in the death of cultured neuronal PC12 cells and sympathetic neurons evoked by exposure to aggregated A beta. The activities of JNK family members increased in neuronal PC12 cells within 2 h of A beta treatment and reached 3--4-fold elevation by 6 h. To test the role of these changes in death caused by A beta, we examined the effects of CEP-1347 (KT7515), an indolocarbazole that selectively blocks JNK activation. Inclusion of CEP-1347 (100--300 nM) in the culture medium effectively blocked the increases in cellular JNK activity caused by A beta and, at similar concentrations, protected both PC12 cells and sympathetic neurons from A beta-evoked-death. Effective protection required addition of CEP-1347 within 2 h of A beta treatment, indicating that the JNK pathway acts relatively proximally and as a trigger in the death mechanism. A dominant-negative c-Jun construct also conferred protection from A beta-evoked death, supporting a model in which JNK activation contributes to death via activation of c-Jun. Finally, CEP-1347 blocked A beta-stimulated activation of caspase-2 and -3, placing these downstream of JNK activation. These observations implicate the JNK pathway as a required element in death evoked by A beta and hence identify it as a potential therapeutic target in AD.  相似文献   
46.
Experimental structural data on the state of substrates bound to class 3 Aldehyde Dehydrogenases (ALDH3A1) is currently unknown. We have utilized molecular mechanics (MM) simulations, in conjunction with new force field parameters for aldehydes, to study the atomic details of benzaldehyde binding to ALDH3A1. Our results indicate that while the nucleophilic Cys243 must be in the neutral state to form what are commonly called near-attack conformers (NACs), these structures do not correlate with increased complexation energy calculated with the MM-Generalized Born Molecular Volume (GBMV) method. The negatively charged Cys243 (thiolate form) of ALDH3A1 also binds benzaldehyde in a stable conformation but in this complex the sulfur of Cys243 is oriented away from benzaldehyde yet yields the most favorable MM-GBMV complexation energy. The identity of the general base, Glu209 or Glu333, in ALDHs remains uncertain. The MM simulations reveal structural and possible functional roles for both Glu209 and Glu333. Structures from the MM simulations that would support either glutamate residue as the general base were further examined with Hybrid Quantum Mechanical (QM)/MM simulations. These simulations show that, with the PM3/OPLS potential, Glu209 must go through a step-wise mechanism to activate Cys243 through an intervening water molecule while Glu333 can go through a more favorable concerted mechanism for the same activation process.  相似文献   
47.
Odor discrimination times and their dependence on stimulus similarity were evaluated to test temporal and spatial models of odor representation in mice. In a go/no-go operant conditioning paradigm, discrimination accuracy and time were determined for simple monomolecular odors and binary mixtures of odors. Mice discriminated simple odors with an accuracy exceeding 95%. Binary mixtures evoking highly overlapping spatiotemporal patterns of activity in the olfactory bulb were discriminated equally well. However, while discriminating simple odors in less than 200 ms, mice required 70-100 ms more time to discriminate highly similar binary mixtures. We conclude that odor discrimination in mice is fast and stimulus dependent. Thus, the underlying neuronal mechanisms act on a fast timescale, requiring only a brief epoch of odor-specific spatiotemporal representations to achieve rapid discrimination of dissimilar odors. The fine discrimination of highly similar stimuli, however, requires temporal integration of activity, suggesting a tradeoff between accuracy and speed.  相似文献   
48.
Ischemic preconditioning confers cardiac protection during subsequent ischemia-reperfusion, in which protein kinase C (PKC) is believed to play an essential role, but controversial data exist concerning the PKC-delta isoform. In an accompanying study (26), we described metabolic changes in PKC-delta knockout mice. We now wanted to explore their effect on early preconditioning. Both PKC-delta(-/-) and PKC-delta(+/+) mice underwent three cycles of 5-min left descending artery occlusion/5-min reperfusion, followed by 30-min occlusion and 2-h reperfusion. Unexpectedly, preconditioning exaggerated ischemia-reperfusion injury in PKC-delta(-/-) mice. Whereas ischemic preconditioning increased superoxide anion production in PKC-delta(+/+) hearts, no increase in reactive oxygen species was observed in PKC-delta(-/-) hearts. Proteomic analysis of preconditioned PKC-delta(+/+) hearts revealed profound changes in enzymes related to energy metabolism, e.g., NADH dehydrogenase and ATP synthase, with partial fragmentation of these mitochondrial enzymes and of the E(2) component of the pyruvate dehydrogenase complex. Interestingly, fragmentation of mitochondrial enzymes was not observed in PKC-delta(-/-) hearts. High-resolution NMR analysis of cardiac metabolites demonstrated a similar rise of phosphocreatine in PKC-delta(+/+) and PKC-delta(-/-) hearts, but the preconditioning-induced increase in phosphocholine, alanine, carnitine, and glycine was restricted to PKC-delta(+/+) hearts, whereas lactate concentrations were higher in PKC-delta(-/-) hearts. Taken together, our results suggest that reactive oxygen species generated during ischemic preconditioning might alter mitochondrial metabolism by oxidizing key mitochondrial enzymes and that metabolic adaptation to preconditioning is impaired in PKC-delta(-/-) hearts.  相似文献   
49.
The publication of scientific articles that receive few or no citations raises questions of the appropriate use of resources as well as ethics. In the case of animal research, the ethics issue extends beyond human patients to nonhuman animals, as the research subjects them to pain and, typically, to death. This study is a citation analysis of animal research conducted at Toronto's Hospital for Sick Children (HSC). Of the 594 publications (1990 to 1995) on animal research by affiliates of HSC, 29% received fewer than 10 citations in a 10-year period. We compare the research history of 13 “best ”and 13 “worst ”HSC scientists. Worst researchers continue to do infrequently cited research. Recommendations indicate how institutions and researchers can become more effective and accountable.  相似文献   
50.
MOTIVATION: Detailed comparison and analysis of the output of DNA gene expression arrays from multiple samples require global normalization of the measured individual gene intensities from the different hybridizations. This is needed for accounting for variations in array preparation and sample hybridization conditions. RESULTS: Here, we present a simple, robust and accurate procedure for the global normalization of datasets generated with single-channel DNA arrays based on principal component analysis. The procedure makes minimal assumptions about the data and performs well in cases where other standard procedures produced biased estimates. It is also insensitive to data transformation, filtering (thresholding) and pre-screening.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号