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   632篇
  免费   81篇
  2022年   5篇
  2021年   14篇
  2020年   9篇
  2019年   18篇
  2018年   13篇
  2017年   13篇
  2016年   17篇
  2015年   37篇
  2014年   36篇
  2013年   30篇
  2012年   51篇
  2011年   36篇
  2010年   24篇
  2009年   25篇
  2008年   32篇
  2007年   27篇
  2006年   30篇
  2005年   28篇
  2004年   35篇
  2003年   16篇
  2002年   19篇
  2001年   5篇
  2000年   6篇
  1999年   7篇
  1998年   4篇
  1997年   4篇
  1996年   7篇
  1995年   5篇
  1994年   4篇
  1993年   6篇
  1992年   7篇
  1991年   5篇
  1990年   6篇
  1988年   4篇
  1987年   8篇
  1984年   6篇
  1983年   5篇
  1979年   8篇
  1978年   3篇
  1977年   7篇
  1976年   5篇
  1974年   11篇
  1973年   7篇
  1972年   7篇
  1971年   5篇
  1969年   4篇
  1967年   3篇
  1965年   3篇
  1958年   3篇
  1944年   3篇
排序方式: 共有713条查询结果,搜索用时 15 毫秒
571.
572.
Aspects of the thermal physiology of the water hyacinth biological control agent Eccritotarsus catarinensis Carvalho (Hemiptera: Miridae) have been extensively investigated over the past 20 years to understand and improve post‐release establishment in the field. Thermal physiology studies predicted that the agent would not establish at a number of cold sites in South Africa, where it has nonetheless subsequently established and thrived. Recently, studies have begun to incorporate the plastic nature of insect thermal physiology into models of agent establishment. This study determined whether season and locality influenced the thermal physiology of two field populations of E. catarinensis, one collected from the hottest site where the agent has established in South Africa, and one from the coldest site. The thermal physiology of E. catarinensis was significantly influenced by season and site, demonstrating a degree of phenotypic plasticity, and that some post‐release local adaptation to climatic conditions has occurred through microevolution. We then determined whether cold acclimation under laboratory conditions was possible. Successfully cold‐acclimated E. catarinensis had a significantly lower critical thermal minimum (CTmin) compared to the field cold‐acclimated population. This suggests that cold acclimation of agents could be conducted in the laboratory before future releases to improve their cold tolerance, thereby increasing their chance of establishment at cold sites and allowing further adaptation to colder climates to occur in the field. Although the thermal tolerance of E. catarinensis is limited by local adaptations to climatic conditions in the native range, the plastic nature of the insect's thermal physiology has allowed it to survive in the very different climatic conditions of the introduced range, and there has been some adaptive change to the insect's thermal tolerance since establishment. This study highlights the importance of plasticity and microevolutionary processes in the success of biological control agents under the novel climatic conditions in the introduced range.  相似文献   
573.
Recurrent HSV-1 ocular disease results from reactivation of latent virus in trigeminal ganglia, often following immunosuppression or exposure to a variety of psychological or physical stressors. HSV-specific CD8+ T cells can block HSV-1 reactivation from latency in ex vivo trigeminal ganglia cultures through production of IFN-gamma. In this study, we establish that either CD8+ T cell depletion or exposure to restraint stress permit HSV-1 to transiently escape from latency in vivo. Restraint stress caused a reduction of TG-resident HSV-specific CD8+ T cells and a functional compromise of those cells that survive. Together, these effects of stress resulted in an approximate 65% reduction of cells capable of producing IFN-gamma in response to reactivating virus. Our findings demonstrate persistent in vivo regulation of latent HSV-1 by CD8+ T cells, and strongly support the concept that stress induces HSV-1 reactivation from latency at least in part by compromising CD8+ T cell surveillance of latently infected neurons.  相似文献   
574.
575.
Gene expression as an intermediate molecular phenotype has been a focus of research interest. In particular, studies of expression quantitative trait loci (eQTL) have offered promise for understanding gene regulation through the discovery of genetic variants that explain variation in gene expression levels. Existing eQTL methods are designed for assessing the effects of common variants, but not rare variants. Here, we address the problem by establishing a novel analytical framework for evaluating the effects of rare or private variants on gene expression. Our method starts from the identification of outlier individuals that show markedly different gene expression from the majority of a population, and then reveals the contributions of private SNPs to the aberrant gene expression in these outliers. Using population-scale mRNA sequencing data, we identify outlier individuals using a multivariate approach. We find that outlier individuals are more readily detected with respect to gene sets that include genes involved in cellular regulation and signal transduction, and less likely to be detected with respect to the gene sets with genes involved in metabolic pathways and other fundamental molecular functions. Analysis of polymorphic data suggests that private SNPs of outlier individuals are enriched in the enhancer and promoter regions of corresponding aberrantly-expressed genes, suggesting a specific regulatory role of private SNPs, while the commonly-occurring regulatory genetic variants (i.e., eQTL SNPs) show little evidence of involvement. Additional data suggest that non-genetic factors may also underlie aberrant gene expression. Taken together, our findings advance a novel viewpoint relevant to situations wherein common eQTLs fail to predict gene expression when heritable, rare inter-individual variation exists. The analytical framework we describe, taking into consideration the reality of differential phenotypic robustness, may be valuable for investigating complex traits and conditions.  相似文献   
576.
The biology of modern Conidae (cone snails)—which includes the hyperdiverse genus Conus—has been intensively studied, but the fossil record of the clade remains poorly understood, particularly within an evolutionary framework. Here, ultraviolet light is used to reveal and characterize the original shell coloration patterns of 28 species of cone snails from three Neogene coral reef-associated deposits from the Cibao Valley, northern Dominican Republic. These fossils come from the upper Miocene Cercado Fm. and lower Pliocene Gurabo Fm., and range in age from about 6.6-4.8 Ma. Comparison of the revealed coloration patterns with those of extant species allow the taxa to be assigned to three genera of cone snails (Profundiconus, Conasprella, and Conus) and at least nine subgenera. Thirteen members of these phylogenetically diverse reef faunas are described as new species. These include: Profundiconus? hennigi, Conasprella (Ximeniconus) ageri, Conus anningae, Conus lyelli, Conus (Atlanticonus?) franklinae, Conus (Stephanoconus) gouldi, Conus (Stephanoconus) bellacoensis, Conus (Ductoconus) cashi, Conus (Dauciconus) garrisoni, Conus (Dauciconus?) zambaensis, Conus (Spuriconus?) kaesleri, Conus (Spuriconus?) lombardii, and Conus (Lautoconus?) carlottae. Each of the three reef deposits contain a minimum of 14–16 cone snail species, levels of diversity that are similar to modern Indo-Pacific reef systems. Finally, most of the 28 species can be assigned to modern clades and thus have important implications for understanding the biogeographic and temporal histories of these clades in tropical America.  相似文献   
577.
Urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for colorectal cancer (CRC) patient survival. However, CRC uPAR expression remains controversial, especially regarding cell types where uPAR is overexpressed (e.g., epithelium (uPARE) or stroma-associated cells (uPARS)) and associated prognostic relevance. In this study, two epitope-specific anti-uPAR monoclonal antibodies (MAbs) could discriminate expression of uPARE from uPARS and were used to examine this association with survival of stages B and C rectal cancer (RC) patients. Using immunohistochemistry, MAbs #3937 and R4 were used to discriminate uPARE from uPARS respectively in the central and invasive frontal regions of 170 stage B and 179 stage C RC specimens. Kaplan-Meier and Cox regression analyses were used to determine association with survival. uPAR expression occurred in both epithelial and stromal compartments with differential expression observed in many cases, indicating uPARE and uPARS have different cellular roles. In the central and invasive frontal regions, uPARE was adversely associated with overall stage B survival (HR = 1.9; p = 0.014 and HR = 1.5; p = 0.031, respectively) reproducing results from previous studies. uPARS at the invasive front was associated with longer stage C survival (HR = 0.6; p = 0.007), reflecting studies demonstrating that macrophage peritumoural accumulation is associated with longer survival. This study demonstrates that different uPAR epitopes should be considered as being expressed on different cell types during tumour progression and at different stages in RC. Understanding how uPARE and uPARS expression affects survival is anticipated to be a useful clinical prognostic marker of stages B and C RC.  相似文献   
578.
579.
The insulin receptor of rat brain is coupled to tyrosine kinase activity   总被引:13,自引:0,他引:13  
Insulin receptors from rat brain were studied for receptor-associated tyrosine kinase activity. In solubilized, lectin-purified receptor preparations, insulin stimulated the phosphorylation of the beta subunit of its receptor as well as of exogenous substrates. Phosphoamino acid analysis of casein phosphorylated by these preparations revealed that 32P incorporation occurred predominantly on tyrosine residues. Receptor and casein phosphorylations were specific for insulin and analogues that also bind to the insulin receptor. The insulin dose response for phosphorylation of brain receptor resembled that reported for the purified insulin receptor from human placenta (Kasuga, M., Fujita-Yamaguchi, Y., Blithe, D.L., and Kahn, C.R. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2137-2141), suggesting similar insulin sensitivity and coupling of the brain receptor kinase. Four polyclonal antisera to the insulin receptor were able to bind and immunoprecipitate the brain receptor; however, only two antisera activated the receptor-associated kinase. Thus, the brain insulin receptor, like the well studied non-neural receptor, is coupled to tyrosine kinase activity, making regulation of cellular events by insulin in neural tissue possible.  相似文献   
580.
The English bulldog: a natural model of sleep-disordered breathing   总被引:10,自引:0,他引:10  
To establish a natural model of sleep-disordered breathing, we investigated respiration during wakefulness and sleep in the English bulldog. This breed is characterized by an abnormal upper airway anatomy, with enlargement of the soft palate and narrowing of the oropharynx. During sleep, the animals had disordered respiration and episodes of O2 desaturation. These were worst in rapid-eye-movement (REM) sleep, with most bulldogs having O2 saturations of less than 90% for prolonged durations. In contrast, control dogs never desaturated. In REM sleep, the bulldogs had episodes of both central and obstructive apnea, the latter being associated with paradoxical movements of the rib cage and abdomen. During wakefulness, the bulldogs were hypersomnolent as evidenced by a shortened sleep latency (mean of 12 min compared with greater than 150 min for controls). This animal model should facilitate studies of the natural history of the sleep apnea syndrome and its complications.  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