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   245篇
  免费   27篇
  2023年   3篇
  2021年   2篇
  2020年   2篇
  2019年   4篇
  2018年   10篇
  2017年   5篇
  2016年   14篇
  2015年   10篇
  2014年   16篇
  2013年   14篇
  2012年   16篇
  2011年   15篇
  2010年   6篇
  2009年   3篇
  2008年   10篇
  2007年   9篇
  2006年   13篇
  2005年   6篇
  2004年   7篇
  2003年   10篇
  2002年   12篇
  2000年   6篇
  1998年   2篇
  1995年   4篇
  1994年   1篇
  1993年   3篇
  1992年   2篇
  1991年   3篇
  1990年   2篇
  1989年   4篇
  1988年   5篇
  1987年   5篇
  1986年   5篇
  1985年   3篇
  1984年   3篇
  1982年   1篇
  1981年   2篇
  1980年   1篇
  1979年   3篇
  1978年   6篇
  1977年   4篇
  1976年   1篇
  1975年   3篇
  1974年   3篇
  1973年   2篇
  1972年   4篇
  1970年   2篇
  1968年   1篇
  1967年   1篇
  1966年   1篇
排序方式: 共有272条查询结果,搜索用时 31 毫秒
41.
42.
43.
Indirect genetic effects (IGEs) are the basis of social interactions among conspecifics, and can affect genetic variation of nonsocial and social traits. We used flour beetles (Tribolium castaneum) of two phenotypically distinguishable populations to estimate genetic (co)variances and the effect of IGEs on three life‐history traits: development time (DT), growth rate (GR), and pupal body mass (BM). We found that GR was strongly affected by social environment with IGEs accounting for 18% of the heritable variation. We also discovered a sex‐specific social effect: male ratio in a group significantly affected both GR and BM; that is, beetles grew larger and faster in male‐biased social environments. Such sex‐specific IGEs have not previously been demonstrated in a nonsocial insect. Our results show that beetles that achieve a higher BM do so via a slower GR in response to social environment. Existing models of evolution in age‐structured or stage‐structured populations do not account for IGEs of social cohorts. It is likely that such IGEs have played a key role in the evolution of developmental plasticity shown by Tenebrionid larvae in response to density. Our results document an important source of genetic variation for GR, often overlooked in life‐history theory.  相似文献   
44.
Tree Genetics & Genomes - Forest and woodland landscape restoration is a key undertaking of renewed interest for forestry and conservation practitioners, but is hampered by the lack of...  相似文献   
45.
Voltage-gated calcium channels (VGCCs) serve as a critical link between electrical signaling and diverse cellular processes in neurons. We have exploited recent advances in genetically encoded calcium sensors and in culture techniques to investigate how the VGCC alpha1 subunit EGL-19 and alpha2/delta subunit UNC-36 affect the functional properties of C. elegans mechanosensory neurons. Using the protein-based optical indicator cameleon, we recorded calcium transients from cultured mechanosensory neurons in response to transient depolarization. We observed that in these cultured cells, calcium transients induced by extracellular potassium were significantly reduced by a reduction-of-function mutation in egl-19 and significantly reduced by L-type calcium channel inhibitors; thus, a main source of touch neuron calcium transients appeared to be influx of extracellular calcium through L-type channels. Transients did not depend directly on intracellular calcium stores, although a store-independent 2-APB and gadolinium-sensitive calcium flux was detected. The transients were also significantly reduced by mutations in unc-36, which encodes the main neuronal alpha2/delta subunit in C. elegans. Interestingly, while egl-19 mutations resulted in similar reductions in calcium influx at all stimulus strengths, unc-36 mutations preferentially affected responses to smaller depolarizations. These experiments suggest a central role for EGL-19 and UNC-36 in excitability and functional activity of the mechanosensory neurons.  相似文献   
46.

Background

The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed.

Methodology/Principal Findings

In 2008, we sent questionnaires to all subjects (aged 18–65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L.

Conclusions/Significance

The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through genetic cascade screening. The attained LDL-C levels were lower than those reported in previous surveys on medication use in FH, which could reflect the effect of more stringent lipid target levels. However, only a minority of the medication users reached the LDL-C target.  相似文献   
47.

Background

To support the development of early warning and surveillance systems of emerging zoonoses, we present a general method to prioritize pathogens using a quantitative, stochastic multi-criteria model, parameterized for the Netherlands.

Methodology/Principal Findings

A risk score was based on seven criteria, reflecting assessments of the epidemiology and impact of these pathogens on society. Criteria were weighed, based on the preferences of a panel of judges with a background in infectious disease control.

Conclusions/Significance

Pathogens with the highest risk for the Netherlands included pathogens in the livestock reservoir with a high actual human disease burden (e.g. Campylobacter spp., Toxoplasma gondii, Coxiella burnetii) or a low current but higher historic burden (e.g. Mycobacterium bovis), rare zoonotic pathogens in domestic animals with severe disease manifestations in humans (e.g. BSE prion, Capnocytophaga canimorsus) as well as arthropod-borne and wildlife associated pathogens which may pose a severe risk in future (e.g. Japanese encephalitis virus and West-Nile virus). These agents are key targets for development of early warning and surveillance.  相似文献   
48.
Studies comparing functional differences in human T-cell leukemia virus type 1 (HTLV-1) clones that mediate distinct outcomes in experimentally infected rabbits, resulted in a dermatopathic smoldering adult T-cell leukemia/lymphoma following chronic infection with HTLV-1 strain RH/K34. During the 3.5 years' follow-up, HTLV-1 skin disease progressed to cutaneous T-cell lymphoma. When infection was passed to several naive rabbits, progressive paraparesis due to myelopathic neurodegeneration, analogous to HTLV-associated myelopathy, resulted in one of 4 transfusion recipients. Similar proviral loads were detected in the two diseases, regardless of stage of progression or tissue compartment of infection. Complete proviral sequences obtained from the donor and affected recipient aligned identically with each other and with the inoculated virus clone. Existence of disparate pathogenic outcomes following infectious transmission further extends the analogy of using rabbits to model human infection and disease. Although the experimental outcomes shown are limited by numbers of animals affected, they mimic the infrequency of HTLV-1 disease and authenticate epidemiological evidence of virus sequence stability regardless of disease phenotype. The findings suggest that further investigation of a possible role for HTLV-1 in some forms of cutaneous T-cell lymphoma is warranted.  相似文献   
49.
The development of genetic tools for non-model organisms has been hampered by cost, but advances in next-generation sequencing (NGS) have created new opportunities. In ecological research, this raises the prospect for developing molecular markers to simultaneously study important genetic processes such as gene flow in multiple non-model plant species within complex natural and anthropogenic landscapes. Here, we report the use of bar-coded multiplexed paired-end Illumina NGS for the de novo development of expressed sequence tag-derived simple sequence repeat (EST-SSR) markers at low cost for a range of 24 tree species. Each chosen tree species is important in complex tropical agroforestry systems where little is currently known about many genetic processes. An average of more than 5,000 EST-SSRs was identified for each of the 24 sequenced species, whereas prior to analysis 20 of the species had fewer than 100 nucleotide sequence citations. To make results available to potential users in a suitable format, we have developed an open-access, interactive online database, tropiTree (http://bioinf.hutton.ac.uk/tropiTree), which has a range of visualisation and search facilities, and which is a model for the efficient presentation and application of NGS data.  相似文献   
50.
M V Kindt  R E Heikkila 《Life sciences》1986,38(16):1459-1462
Pretreatment of mice with the potent and selective monoamine oxidase B (MAO-B) inhibitor MDL 72145 ((E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine) protected against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice treated with MDL 72145 prior to MPTP did not exhibit the decrement in the neostriatal content of dopamine and its metabolites normally seen after MPTP administration. This observation adds further support to the concept that the oxidation of MPTP by MAO-B to its corresponding pyridinium analog, 1-methyl-4-phenylpyridinium (MPP+), is an important feature of the neurotoxic process.  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