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   2739篇
  免费   161篇
  2023年   19篇
  2022年   28篇
  2021年   108篇
  2020年   57篇
  2019年   73篇
  2018年   88篇
  2017年   88篇
  2016年   121篇
  2015年   176篇
  2014年   199篇
  2013年   226篇
  2012年   217篇
  2011年   198篇
  2010年   143篇
  2009年   105篇
  2008年   135篇
  2007年   109篇
  2006年   106篇
  2005年   90篇
  2004年   102篇
  2003年   77篇
  2002年   80篇
  2001年   61篇
  2000年   39篇
  1999年   37篇
  1998年   21篇
  1997年   13篇
  1996年   8篇
  1995年   5篇
  1994年   5篇
  1993年   8篇
  1992年   17篇
  1991年   13篇
  1990年   10篇
  1989年   10篇
  1988年   8篇
  1987年   10篇
  1986年   7篇
  1985年   5篇
  1984年   6篇
  1983年   8篇
  1980年   6篇
  1979年   5篇
  1976年   3篇
  1975年   3篇
  1971年   3篇
  1970年   4篇
  1969年   9篇
  1968年   5篇
  1965年   4篇
排序方式: 共有2900条查询结果,搜索用时 109 毫秒
91.
The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (α = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05–2.23), in children from families with a monthly household income ≤US$312.50 (OR = 2.38, 95%CI: 1.65–3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07–2.23). Lesion activity was significantly associated with mother’s schooling ≤ 8 years (OR = 2.15, 95%CI: 1.15–4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother’s schooling.  相似文献   
92.

Background

Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.

Methods and Findings

Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications.

Conclusions

Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease.  相似文献   
93.
94.
Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4''-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.  相似文献   
95.
96.

Background

Accurate quantitative assessment of infection with soil transmitted helminths and protozoa is key to the interpretation of epidemiologic studies of these parasites, as well as for monitoring large scale treatment efficacy and effectiveness studies. As morbidity and transmission of helminth infections are directly related to both the prevalence and intensity of infection, there is particular need for improved techniques for assessment of infection intensity for both purposes. The current study aimed to evaluate two multiplex PCR assays to determine prevalence and intensity of intestinal parasite infections, and compare them to standard microscopy.

Methodology/Principal Findings

Faecal samples were collected from a total of 680 people, originating from rural communities in Timor-Leste (467 samples) and Cambodia (213 samples). DNA was extracted from stool samples and subject to two multiplex real-time PCR reactions the first targeting: Necator americanus, Ancylostoma spp., Ascaris spp., and Trichuris trichiura; and the second Entamoeba histolytica, Cryptosporidium spp., Giardia. duodenalis, and Strongyloides stercoralis. Samples were also subject to sodium nitrate flotation for identification and quantification of STH eggs, and zinc sulphate centrifugal flotation for detection of protozoan parasites. Higher parasite prevalence was detected by multiplex PCR (hookworms 2.9 times higher, Ascaris 1.2, Giardia 1.6, along with superior polyparasitism detection with this effect magnified as the number of parasites present increased (one: 40.2% vs. 38.1%, two: 30.9% vs. 12.9%, three: 7.6% vs. 0.4%, four: 0.4% vs. 0%). Although, all STH positive samples were low intensity infections by microscopy as defined by WHO guidelines the DNA-load detected by multiplex PCR suggested higher intensity infections.

Conclusions/Significance

Multiplex PCR, in addition to superior sensitivity, enabled more accurate determination of infection intensity for Ascaris, hookworms and Giardia compared to microscopy, especially in samples exhibiting polyparasitism. The superior performance of multiplex PCR to detect polyparasitism and more accurately determine infection intensity suggests that it is a more appropriate technique for use in epidemiologic studies and for monitoring large-scale intervention trials.  相似文献   
97.
Although the mechanism of action of antimicrobial peptides (AMPs) is not clear, they can interact electrostatically with the cell membranes of microorganisms. New ocellatin‐PT peptides were recently isolated from the skin secretion of Leptodactylus pustulatus. The secondary structure of these AMPs and their effect on Leishmania infantum cells, and on different lipid surface models was characterized in this work. The results showed that all ocellatin‐PT peptides have an α‐helix structure and five of them (PT3, PT4, PT6 to PT8) have leishmanicidal activity; PT1 and PT2 affected the cellular morphology of the parasites and showed greater affinity for leishmania and bacteria‐mimicking lipid membranes than for those of mammals. The results show selectivity of ocellatin‐PTs to the membranes of microorganisms and the applicability of biophysical methods to clarify the interaction of AMPs with cell membranes.  相似文献   
98.
The sets of species in animal and plant communities often comprise nested subsets of the species in broader communities. Although most mechanisms causing nested patterns are known and have been demonstrated for different environments and taxa, how amphibian communities are structured in ephemeral ponds in tropical disturbed landscapes remains unknown. We investigated if pond size, duration, presence of trees (local factors), and the proportion of forest cover surrounding ponds (landscape factor) affect anuran species richness and composition, and if pond assemblages showed a nested pattern. We sampled 11 ephemeral ponds in a pasture matrix near a large Atlantic Forest remnant in Brazil and measured local and landscape variables inside two buffer zones around each pond (100 and 500 m). We marked 1514 individuals from 23 anuran species, and found that richness in ponds ranged from 3–14 species. Both local and landscape factors explained frog species richness in the sampled ponds, and seemed to affect community composition. Frog communities occurred in a non‐nested pattern, contrary to our expectations: species found in poor subsets were not found in larger, more complex ponds. Local and landscape characteristics create a variety of environments in ephemeral ponds, even in impoverished ones; these characteristics restrict pond occupancy for some species, and result in a non‐nested pattern.  相似文献   
99.
Planta - In the present study, miRNA precursors in the genomes of three palm species were identified. Analyzes of sequence conservation and biological function of their putative targets contribute...  相似文献   
100.
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