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   1880篇
  免费   89篇
  国内免费   1篇
  1970篇
  2023年   21篇
  2022年   29篇
  2021年   70篇
  2020年   52篇
  2019年   51篇
  2018年   68篇
  2017年   66篇
  2016年   78篇
  2015年   110篇
  2014年   107篇
  2013年   165篇
  2012年   131篇
  2011年   135篇
  2010年   95篇
  2009年   61篇
  2008年   97篇
  2007年   86篇
  2006年   96篇
  2005年   79篇
  2004年   74篇
  2003年   60篇
  2002年   45篇
  2001年   11篇
  2000年   9篇
  1999年   16篇
  1998年   12篇
  1997年   10篇
  1996年   8篇
  1995年   4篇
  1994年   5篇
  1993年   11篇
  1992年   9篇
  1991年   9篇
  1990年   4篇
  1989年   7篇
  1988年   3篇
  1987年   3篇
  1986年   5篇
  1985年   4篇
  1984年   9篇
  1983年   7篇
  1982年   6篇
  1980年   7篇
  1979年   3篇
  1978年   3篇
  1977年   3篇
  1974年   2篇
  1973年   3篇
  1962年   2篇
  1958年   3篇
排序方式: 共有1970条查询结果,搜索用时 15 毫秒
991.
Few field studies have investigated how changes at one trophic level can affect the invasibility of other trophic levels. We examined the hypothesis that the spread of an introduced alga in disturbed seagrass beds with degraded canopies depends on the depletion of large consumers. We mimicked the degradation of seagrass canopies by clipping shoot density and reducing leaf length, simulating natural and anthropogenic stressors such as fish overgrazing and water quality. Caulerpa racemosa was transplanted into each plot and large consumers were excluded from half of them using cages. Potential cage artifacts were assessed by measuring irradiance, scouring by leaf movement, water flow, and sedimentation. Algal invasion of the seagrass bed differed based on the size of consumers. The alga had higher cover and size under the cages, where the seagrass was characterized by reduced shoot density and canopy height. Furthermore, canopy height had a significant effect depending on canopy density. The alteration of seagrass canopies increased the spread of C. racemosa only when large consumers were absent. Our results suggest that protecting declining habitats and/or restoring fish populations will limit the expansion of C. racemosa. Because MPAs also enhance the abundance and size of fish consuming seagrass they can indirectly promote algal invasion. The effects of MPAs on invasive species are context dependent and require balancing opposing forces, such as the conservation of seagrass canopy structure and the protection of fish grazing the seagrass.  相似文献   
992.
Neutral and cationic tripyridylporphyrin-D-galactose conjugates were synthesized and their antiviral activity against herpes simplex virus type 1 (HSV-1) was evaluated. At non-cytotoxic concentrations the studied compounds show significant antiviral activity after photoactivation. The influence of photoactivation on drug treated cells was also analyzed, at different times of infection with HSV-1, for a neutral (1b) and a cationic glycoporphyrin (3b) derivative. The results show that the inhibition of the viral yield is more dependent on photoactivation for compound 1b than for compound 3b. These two compounds also differ in the inhibitory effect during the viral replicative cycle: while compound 3b inhibits the viral yield at all the addition times assayed, compound 1b is more efficient in later times of infection.  相似文献   
993.
Tecoma stans (L.) Kunth is an exotic plant in Brazil, commonly distributed in urban areas, which is considered an invasive species in crop and pasture areas. In this study, the floral biology and the behavior of bees in flowers of T. stans from three urban areas in southeastern Brazil were investigated. In all study sites, T. stans was an important food resource to the Apoidea to 48 species of bees. Centris tarsata Smith and Exomalopsis fulvofasciata Smith (Hymenoptera: Apidae) were the effective pollinators more abundant, while Scaptotrigona depilis Moure (Hymenoptera: Apidae) was the more frequent robber species. The most part of T. stans visitors (87.5%) exploited exclusively nectar, which varied in sugar concentration depending on the day period and flower phase. In all flower stages, higher averages of nectar concentration (26.4% to 32.7%) occurred from 10 am to 2 pm. The presence of osmophore in the petals and protandry were detected. In two urban areas the number of visitors varied significantly during the day. The greatest abundance of pollinators occurred when pollen availability was higher and flowers showed receptive stigma, which could be contributing to the reproductive success of T. stans. The results indicate that the production of fruits increased in plants that received a higher number of effective pollinators.  相似文献   
994.
We analyzed the whole-cell protein content of gastrocnemius muscles from rats in different thyroid states. Twenty differentially expressed proteins were unambiguously identified. They were involved in substrates and energy metabolism, stress response, cell structure, and gene expression. This study represents the first systematic identification of thyroid state-induced changes in the skeletal muscle protein-expression profile and reveals new cellular pathways as targets for thyroid hormone action.  相似文献   
995.
Summary We investigated the in vivo effects of cyclophosphamide (CY) on interleukin-2(IL-2)-induced cytolytic function and spleen cell immunophenotype. Pretreatment of A/J mice with CY (25 mg/kg or 75 mg/kg) i.p. on days –10 and –15 followed by IL-2 (50 000 U i.p. on days 0 to +3) resulted in increased lysis of YAC-1 target cells compared to the group receiving IL-2 without previous CY therapy. In contrast, when CY was given on day -5, the cytotoxicity against YAC-1 was not enhanced. Phenotypic analysis of splenocytes obtained from mice treated with CY on day –10 or –15 revealed a relative decrease in L3T4- and Lyt2-positive T cells. In vivo depletion of natural killer (NK) cells by anti-asialoGM1, prior to IL-2 therapy, abrogated the enhancing effect of CY on cytolysis while in vivo elimination of T cells by anti-L3T4 and anti-Lyt2 monoclonal antibodies did not, indicating that in the absence of T cell antigenic challenge, the increased cytolytic function after CY administration is probably mediated through NK cells. These findings provide evidence that CY may be used more effectively in IL-2-based immunotherapy protocols, if consideration is given to timing of CY and IL-2 administration.Supported in part by the Children's Cancer Research Fund, the Concern II Foundation, RO1-CA-21 737, NO1-AI-85 002 and a contract to the University of Minnesota from OncoTherapeutics Inc. Dr. E. Katsanis is supported by a fellowship from the Medical Research Council of Canada. Dr. P. M. Anderson is supported by a Clinical Oncology Career Development Award from the American Cancer Society. This is paper no. 550 of the Immunobiology Research Center  相似文献   
996.
Moniliophthora perniciosa and Moniliophthora roreri are phytopathogenic basidiomycete species that infect cacao causing two important diseases in this crop: “Witches’ Broom” and “Frosty Pod Rot”, respectively. The ability of species from this genus (Moniliophthora) to cause disease is exceptional in the family Marasmiaceae. Species in closely related genera including, Marasmius, Crinipellis, and Chaetocalathus, are mainly saprotrophs and are not known to cause disease. In this study, the possibility that this phytopathogenic lifestyle has been acquired by horizontal gene transfer (HGT) was investigated. A stringent genome comparison pipeline was used to identify potential genes that have been obtained by Moniliophthora through HGT. This search led to the identification of three genes: a metallo-dependent hydrolase (MDH), a mannitol phosphate dehydrogenase (MPDH), and a family of necrosis-inducing proteins (NEPs). Phylogenetic analysis of these genes suggests that Moniliophthora acquired NEPs from oomycetes, MDH from actinobacteria and MPDH from firmicutes. Based on the known gene functions and on previous studies of M. perniciosa infection and development, a correlation between gene acquisition and the evolution of the phytopathogenic genus Moniliophthora can be postulated.  相似文献   
997.
Prostate cancer (PC) is the most frequently diagnosed cancer in men. The acquisition of castration-resistant (CR) phenotype is associated with the activation of signaling pathways mediated by growth factors. The TGFβ1 and its receptors have an important role in tumor progression, being the pro-apoptotic function modulated by the expression of TGFBR2. A single nucleotide polymorphism -875 G > A in TGFBR2 gene has been described, which may influence the expression levels of the receptor. Our purpose was to investigate the potential role of TGFBR2-875G>A in PC risk and in the response to androgen deprivation therapy (ADT). TGFBR2-875G>A polymorphism was studied by allelic discrimination using real-time polymerase chain reaction (PCR) in 891 patients with PC and 874 controls. A follow-up study was undertaken to evaluate response to ADT. The TGFBR2 and SMAD7 mRNA expression were analyzed by a quantitative real-time PCR. We found that TGFBR2-875GG homozygous patients present lower expression levels of TGFBR2 mRNA (AA/AG: 2-ΔΔCT =1.5, P=0.016). GG genotype was also associated with higher Gleason grade (OR=1.51, P=0.019) and increased risk of an early relapse after ADT (HR=1.47, P=0.024). The concordance (c) index analysis showed that the definition of profiles that contains information regarding tumor characteristics associated with genetic information present an increased capacity to predict the risk for CR development (c-index model 1: 0.683 vs model 2: 0.736 vs model 3: 0.746 vs model 4: 0.759). The TGFBR2-875G>A contribution to an early relapse in ADT patients, due to changes in mRNA expression, supports the involvement of TGFβ1 pathway in CRPC. Furthermore, according to our results, we hypothesize the potential benefits of the association of genetic information in predictive models of CR development.  相似文献   
998.
Macropelopiini is a widely distributed tribe of Tanypodinae, with immature stages inhabiting cool seeps, springs, and small streams. The present study evaluated the monophyly and the supporting synapomorphies within a phylogenetic context for the first time for Macropelopiini. The monophyly and the intergeneric relationships were tested by morphological evidence in a cladistic framework, and the information gained from each homoplastic character was evaluated. The monophyly of Macropelopiini is corroborated through the objective synapomorphy ‘outer fringe decreasing from base to apex ending in small spines’ in the pupa, and the subjective synapomorphies ‘tibial spurs with main teeth and short lateral tooth’ in males and ‘dorsal setae arising from prominent tubercles’ in the pupa. Fittkauimyia Karunakaran, 1969 is excluded from Macropelopiini, Gressitius Sublette & Wirth, 1980 is established as a junior synonym of Alotanypus Roback, 1971, and the new combination A lotanypus antarcticus comb. nov. is proposed. Character combination, mainly through the use of the characters with informative taxonomical value, remains an efficient tool to diagnose the Macropelopiini genera. The new genus Paggipelopia gen. nov. for P aggipelopia spaccesii gen. et sp. nov. is erected and the emendation of the species diagnosis of Wuelkerella toncekensis Añón Suárez & Sublette, 2012 is conducted. © 2015 The Linnean Society of London  相似文献   
999.
1000.
The resumption of tuberculosis led to an increased need to understand the molecular mechanisms of drug action and drug resistance, which should provide significant insight into the development of newer compounds. Isoniazid (INH), the most prescribed drug to treat TB, inhibits an NADH-dependent enoyl-acyl carrier protein reductase (InhA) that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. InhA is the major target of the mode of action of isoniazid. INH is a pro-drug that needs activation to form the inhibitory INH-NAD adduct. Missense mutations in the inhA structural gene have been identified in clinical isolates of Mycobacterium tuberculosis resistant to INH. To understand the mechanism of resistance to INH, we have solved the structure of two InhA mutants (I21V and S94A), identified in INH-resistant clinical isolates, and compare them to INH-sensitive WT InhA structure in complex with the INH-NAD adduct. We also solved the structure of unliganded INH-resistant S94A protein, which is the first report on apo form of InhA. The salient features of these structures are discussed and should provide structural information to improve our understanding of the mechanism of action of, and resistance to, INH in M. tuberculosis. The unliganded structure of InhA allows identification of conformational changes upon ligand binding and should help structure-based drug design of more potent antimycobacterial agents.  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