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   1483篇
  免费   128篇
  2023年   6篇
  2022年   17篇
  2021年   28篇
  2020年   28篇
  2019年   27篇
  2018年   39篇
  2017年   48篇
  2016年   50篇
  2015年   69篇
  2014年   79篇
  2013年   107篇
  2012年   117篇
  2011年   94篇
  2010年   71篇
  2009年   68篇
  2008年   84篇
  2007年   61篇
  2006年   81篇
  2005年   74篇
  2004年   56篇
  2003年   52篇
  2002年   51篇
  2001年   37篇
  2000年   33篇
  1999年   40篇
  1998年   10篇
  1997年   15篇
  1996年   18篇
  1995年   15篇
  1994年   9篇
  1993年   10篇
  1992年   15篇
  1991年   15篇
  1990年   15篇
  1989年   3篇
  1988年   5篇
  1987年   11篇
  1986年   11篇
  1985年   10篇
  1984年   8篇
  1983年   2篇
  1978年   5篇
  1977年   2篇
  1974年   2篇
  1973年   2篇
  1972年   1篇
  1971年   1篇
  1968年   1篇
  1967年   2篇
  1964年   1篇
排序方式: 共有1611条查询结果,搜索用时 125 毫秒
991.
Galphimia glauca produces compounds denominated galphimines (galphimine‐A, galphimine‐B and galphimine‐E). Due to their important anxiolytic activity, we initiated in vitro cultures of the species with the purpose of developing a biotechnological process for obtaining galphimines. In this work, we stimulated the biosynthesis and excretion of galphimines with two‐phase batch‐type cell suspension cultures of G. glauca. The effect of nutritional variation and the 2,4‐dichlorophenoxy acetic acid added to Murashige & Skoog(MS) culture medium was evaluated. Later, we evaluated the effect of the stimulation with calcium and methyl jasmonate (MeJ). The greatest production of galphimine‐B (3.39 × 10?5 g/L day?1) was obtained on day 40 of kinetics, and induced by a treatment containing concentrations of nitrates and phosphate that are double of those normally used in MS medium, without sucrose but with added 2,4‐dichlorophenoxy acetic acid (4 mg/L). Time of galphimine‐B biosynthesis diminished due to the effect of MeJ in combination with calcium, and induced the excretion (100%) of galphimine‐B (6.35 × 10?5 g/L day?1) into the culture medium. Thus, the use of calcium and MeJ comprises a viable alternative to stimulate the production and excretion of galphimine‐B and galphimine‐A in batch‐type cultures of G. glauca in modified MS medium. Once optimized, the production of the anxiolytic compounds can be scaled up to the industrial level.  相似文献   
992.

Background

The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson’s disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown.

Results

By taking advantage of transgenic labeling, laser capture microdissection coupled to nano Cap-Analysis of Gene Expression (nanoCAGE) technology on isolated A9 and A10 cells, we found that a subset of Olfactory Receptors (OR)s is expressed in mDA neurons. Gene expression analysis was integrated with the FANTOM5 Helicos CAGE sequencing datasets, showing the presence of these ORs in selected tissues and brain areas outside of the olfactory epithelium. OR expression in the mesencephalon was validated by RT-PCR and in situ hybridization. By screening 16 potential ligands on 5 mDA ORs recombinantly expressed in an heterologous in vitro system, we identified carvone enantiomers as agonists at Olfr287 and able to evoke an intracellular Ca2+ increase in solitary mDA neurons. ORs were found expressed in human SN and down-regulated in PD post mortem brains.

Conclusions

Our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-729) contains supplementary material, which is available to authorized users.  相似文献   
993.
Dispersal and local patterns of adaptation play a major role on the ecological and evolutionary trajectory of natural populations. In this study, we employ a combination of genetic (25 microsatellite markers) and field‐based information (seven study years) to analyse the impact of immigration and local patterns of adaptation in two nearby (< 7 km) blue tit (Cyanistes caeruleus) populations. We used genetic assignment analyses to identify immigrant individuals and found that dispersal rate is female‐biased (72%). Data on lifetime reproductive success indicated that immigrant females produced fewer local recruits than their philopatric counterparts whereas immigrant males recruited more offspring than those that remained in their natal location. In spite of the considerably higher immigration rates of females, our results indicate that, in absolute terms, their demographic and genetic impact in the receiving populations is lower than that in immigrant males. Immigrants often brought novel alleles into the studied populations and a high proportion of them were transmitted to their recruits, indicating that the genetic impact of immigrants is not ephemeral. Although only a few kilometres apart, the two study populations were genetically differentiated and showed strong divergence in different phenotypic and life‐history traits. An almost absent inter‐population dispersal, together with the fact that both populations receive immigrants from different source populations, is probably the main cause of the observed pattern of genetic differentiation. However, phenotypic differentiation (PST) for all the studied traits greatly exceeded neutral genetic differentiation (FST), indicating that divergent natural selection is the prevailing factor determining the evolutionary trajectory of these populations. Our study highlights the importance of integrating individual‐ and population‐based approaches to obtain a comprehensive view about the role of dispersal and natural selection on structuring the genotypic and phenotypic characteristics of natural populations.  相似文献   
994.
995.

Background

Emotional intelligence (EI) can be broadly defined as the ability to cope with environmental demands. In the scientific research, however, there is not a univocal precise definition of EI and recent articles have underlined the necessity to explore its biological basis to advance understanding of the construct. The aim of study was to investigate if the antioxidant network may be associated with typical-performance or trait EI.

Methods

The study group consisted of 50 women (age, M = 25.10, SD = 3.87). Super Oxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR), and Glutathione Peroxidase (GPx) activities were evaluated on proteins extracted from Peripheral Blood Mononuclear Cells. Participants completed the Italian version of the EQ-i (Bar-On, 1997) as a measure of trait EI.

Results

We observed positive and significant correlations between some biological variables and EQ-i scores, and a significant predictive effect of CAT activity when controlling for related biological variables, age, and smoking.

Conclusions

Our preliminary study suggests that the antioxidant network may constitute some of trait EI''s biological basis. In particular, CAT and the SOD/CAT ratio could be two biological variables involved in some specific components of EI.  相似文献   
996.
Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as “variants of uncertain significance”, being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.  相似文献   
997.

Objective

We used demographic and clinical data to design practical classification models for prediction of neurocognitive impairment (NCI) in people with HIV infection.

Methods

The study population comprised 331 HIV-infected patients with available demographic, clinical, and neurocognitive data collected using a comprehensive battery of neuropsychological tests. Classification and regression trees (CART) were developed to obtain detailed and reliable models to predict NCI. Following a practical clinical approach, NCI was considered the main variable for study outcomes, and analyses were performed separately in treatment-naïve and treatment-experienced patients.

Results

The study sample comprised 52 treatment-naïve and 279 experienced patients. In the first group, the variables identified as better predictors of NCI were CD4 cell count and age (correct classification [CC]: 79.6%, 3 final nodes). In treatment-experienced patients, the variables most closely related to NCI were years of education, nadir CD4 cell count, central nervous system penetration-effectiveness score, age, employment status, and confounding comorbidities (CC: 82.1%, 7 final nodes). In patients with an undetectable viral load and no comorbidities, we obtained a fairly accurate model in which the main variables were nadir CD4 cell count, current CD4 cell count, time on current treatment, and past highest viral load (CC: 88%, 6 final nodes).

Conclusion

Practical classification models to predict NCI in HIV infection can be obtained using demographic and clinical variables. An approach based on CART analyses may facilitate screening for HIV-associated neurocognitive disorders and complement clinical information about risk and protective factors for NCI in HIV-infected patients.  相似文献   
998.
Because of the serious effects of pollution on water supply much closer attention has been paid to water quality than to other aspects of river integrity. However, channel form and water flow are relevant components of river health, and recent evidences show that their impairment threatens the services derived from them. In this article, we review the literature on the effects of common hydromorphological impacts (channel modification and flow modification) on the functioning of river ecosystems. There are evidences that even light hydromorphological impacts can have deep effects on ecosystem functioning, and that different functional variables differ in their responses. Three criteria (relevance, scale and sensitivity) in the selection of functional variables are suggested as a guide for the river scientists and managers to assess the ecological impacts of hydromorphological modifications.  相似文献   
999.
1000.
Senescence can be defined as the entire set of age-related changes that affect both vitality and function, one of which is within-individual age-related decline in reproduction. This factor is crucial for population persistence, because the senescence of individuals of a population can increase the likelihood of local extinction. Using simulations based on long-term information on a small metapopulation of a long-lived bird species, we highlight two mechanisms able to engender senescence in both breeders and floaters (i.e. non-breeding individuals) of the same population. We define 'floater shortage senescence' as breeder senescence due to low juvenile replacement rates because of high floater mortality during dispersal. Less obviously, senescence can also occur with very low floater mortality rates, and when breeding populations are remarkably free from factors that could cause catastrophic population decimation. In this scenario, low mortality in reproductive areas results in territory owners in breeding populations being characterised by progressively older breeding individuals, and old individuals waiting for a breeding opportunity: a phenomenon we refer to as the 'Florida effect'. Consistent with current views that adaptive death plays a crucial role in population dynamics, it seems reasonable to suppose that, under stable environmental conditions, the evolution of some mating mechanisms could limit the senescence of breeding individuals in a population, allowing the pool of breeding individuals to be refreshed by selection of younger breeders.  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