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   915篇
  免费   54篇
  2023年   5篇
  2022年   21篇
  2021年   35篇
  2020年   20篇
  2019年   17篇
  2018年   17篇
  2017年   11篇
  2016年   29篇
  2015年   55篇
  2014年   58篇
  2013年   59篇
  2012年   50篇
  2011年   76篇
  2010年   44篇
  2009年   45篇
  2008年   49篇
  2007年   57篇
  2006年   43篇
  2005年   38篇
  2004年   31篇
  2003年   26篇
  2002年   23篇
  2001年   12篇
  2000年   8篇
  1999年   6篇
  1998年   4篇
  1997年   4篇
  1995年   4篇
  1994年   3篇
  1993年   7篇
  1992年   4篇
  1991年   8篇
  1990年   6篇
  1989年   6篇
  1988年   6篇
  1987年   3篇
  1986年   5篇
  1985年   3篇
  1983年   6篇
  1982年   3篇
  1981年   4篇
  1980年   8篇
  1978年   6篇
  1972年   4篇
  1970年   6篇
  1969年   3篇
  1966年   2篇
  1965年   2篇
  1961年   3篇
  1960年   2篇
排序方式: 共有969条查询结果,搜索用时 773 毫秒
951.
The maintenance of reproductive isolation in the face of gene flow is a particularly contentious topic, but differences in reproductive behavior may provide the key to explaining this phenomenon. However, we do not yet fully understand how behavior contributes to maintaining species boundaries. How important are behavioral differences during reproduction? To what extent does assortative mating maintain reproductive isolation in recently diverged populations and how important are “magic traits”? Assortative mating can arise as a by‐product of accumulated differences between divergent populations as well as an adaptive response to contact between those populations, but this is often overlooked. Here we address these questions using recently described species pairs of three‐spined stickleback (Gasterosteus aculeatus), from two separate locations and a phenotypically intermediate allopatric population on the island of North Uist, Scottish Western Isles. We identified stark differences in the preferred nesting substrate and courtship behavior of species pair males. We showed that all males selectively court females of their own ecotype and all females prefer males of the same ecotype, regardless of whether they are from species pairs or allopatric populations. We also showed that mate choice does not appear to be driven by body size differences (a potential “magic trait”). By explicitly comparing the strength of these mating preferences between species pairs and single‐ecotype locations, we were able to show that present levels of assortative mating due to direct mate choice are likely a by‐product of other adaptations between ecotypes, and not subject to obvious selection in species pairs. Our results suggest that ecological divergence in mating characteristics, particularly nesting microhabitat may be more important than direct mate choice in maintaining reproductive isolation in stickleback species pairs.  相似文献   
952.
953.
Summary The claims made byCusters in connection with the disproportionate yields of ethanol and carbon dioxide from the fermentative dissimilation of glucose in yeast water byBrett. claussenii were investigated forBrett. intermedius. All results obtained showed thatBrett. intermedius produced the normal equimolar amounts of ethanol and carbon dioxide, irrespective of whether the studies were conducted in yeast water or in dilute yeast water supplemented with a suitable nitrogen source. Re-investigation of the fermentative dissimilation of glucose in yeast water byBrett. claussenii gave the same results as withBrett. intermedius. Part I and II: Antonie van Leeuwenhoek24, 239, 1958;25, 145, 1959.  相似文献   
954.
955.
The Drosophila brain consists of a relatively small number of invariant, genetically determined lineages which provide a model to study the relationship between gene function and neuronal architecture. In following this long‐term goal, we reconstruct the morphology (projection pattern and connectivity) and gene expression patterns of brain lineages throughout development. In this article, we focus on the secondary phase of lineage morphogenesis, from the reactivation of neuroblast proliferation in the first larval instar to the time when proliferation ends and secondary axon tracts have fully extended in the late third larval instar. We have reconstructed the location and projection of secondary lineages at close (4 h) intervals and produced a detailed map in the form of confocal z‐projections and digital three‐dimensional models of all lineages at successive larval stages. Based on these reconstructions, we could compare the spatio‐temporal pattern of axon formation and morphogenetic movements of different lineages in normal brain development. In addition to wild type, we reconstructed lineage morphology in two mutant conditions. (1) Expressing the construct UAS‐p35 which rescues programmed cell death we could systematically determine which lineages normally lose hemilineages to apoptosis. (2) so‐Gal4‐driven expression of dominant‐negative EGFR ablated the optic lobe, which allowed us to conclude that the global centrifugal movement normally affecting the cell bodies of lateral lineages in the late larva is causally related to the expansion of the optic lobe, and that the central pattern of axonal projections of these lineages is independent of the presence or absence of the optic lobe. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 434–451, 2016  相似文献   
956.
In the past 50 years, disease burden has steadily shifted from infectious disease to cancer. Standard chemotherapy has long been the mainstay of cancer medical management, and despite vast efforts towards more targeted and personalized drug therapy, many cancers remain refractory to treatment, with high rates of relapse and poor prognosis. Recent dramatic immunotherapy clinical trials have demonstrated that engineering T-cells with chimeric antigen receptors (CARs) to target CD19 can lead to complete remission in relapsed or refractory B-cell malignancies, generating a great deal of enthusiasm in the field. Here we provide a comprehensive overview of the history of adoptive T-cell therapy, including CARs, in solid tumors as well as hematologic malignancies. CAR therapy has the potential to fundamentally transform cancer treatment with specific and even personalized targeting of tissue- and tumor-specific antigens. However, before CARs become standard first-line treatment modalities, critical issues regarding efficacy, combinatorial regimens, and mechanisms of treatment failure and toxicity will need to be addressed.  相似文献   
957.

The objective of this study was to determine clinical-epidemiological characteristics of the patients and the genetic characteristics of carbapenemase KPC-3-producing Klebsiella pneumoniae isolates belonging to sequence type ST258. The eligible study population was all patients with isolates detected between October 2015 and March 2017. Clinical–epidemiological and microbiological data were gathered on risk factors associated with infection by this clone. Antimicrobial susceptibility was determined using MicroScan system and diffusion in agar. Genes encoding carbapenemases were detected using PCR and Sanger sequencing. The sequence type was assigned by MLST, and the genetic relationship among clinical isolates was determined by pulsed field electrophoresis and by analysis of the genetic environment. The study included 23 individuals with isolates of KPC-3/ST258; the mean age was 77 year, and mean stay pre-isolation was 32 days; 81% received empirical antimicrobial treatment. Isolates were only susceptible to gentamicin (CIM?≤?2 mg/L), tigecycline (CIM?≤?1 mg/L), and colistin (CIM?≤?2 mg/L). The isolates belonged to ST258, with five pulse types or subgroups. All isolates showed amplification of KPC, which was identified as KPC-3 variant. Gene blaKPC-3 was flanked by insertion sequences Kpn6 and Kpn7 within Tn4401 transposon isoform a. We report, for the first time in Spain, an 18-month outbreak by KPC-3-producing ST258 K. pneumoniae. Its acquisition was associated with a history of antimicrobial therapy, with three treatment options, and with high mortality. The detection of different pulse types is attributable to different introductions of the clone in our setting, supporting the need for multi-resistant isolate surveillance studies.

  相似文献   
958.
Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking domain and a plant-related senescence domain involved in cytokinesis and mitochondrial physiology, respectively—have been defined. We have shown that overexpressed spartin binds to the Ile44 hydrophobic pocket of ubiquitin, suggesting spartin might contain a ubiquitin-binding domain. In the present study, we demonstrate that spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using short hairpin RNA, we knocked down spartin in RAW264.7 cells and found that DALIS frequency decreased; conversely, overexpression of spartin increased the percentage of cells containing DALIS. Using nuclear magnetic resonance spectroscopy, we characterized spartin''s UBR and defined the UBR''s amino acids that are key for ubiquitin binding. We also found that spartin, via the UBR, binds Lys-63–linked ubiquitin chains but does not bind Lys-48–linked ubiquitin chains. Finally, we demonstrate that spartin''s role in DALIS formation depends on key residues within its UBR.  相似文献   
959.
960.
Nuclear pores in the apoptotic cell   总被引:2,自引:0,他引:2  
Summary During apoptosis, nuclear pores undergo strong modifications, which are described here in five different apoptotic models. Conventional electron microscopy, supported by freeze-fracture analysis, showed a constant migration of nuclear pores towards the diffuse chromatin areas. In contrast, dense chromatin areas appear pore-free and are frequently surrounded by strongly dilated cisternae. A possible functional significance of this pore behaviour during apoptosis is discussed.  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