全文获取类型
收费全文 | 1738篇 |
免费 | 79篇 |
国内免费 | 36篇 |
出版年
2024年 | 4篇 |
2023年 | 25篇 |
2022年 | 44篇 |
2021年 | 45篇 |
2020年 | 37篇 |
2019年 | 34篇 |
2018年 | 43篇 |
2017年 | 27篇 |
2016年 | 27篇 |
2015年 | 32篇 |
2014年 | 95篇 |
2013年 | 78篇 |
2012年 | 40篇 |
2011年 | 55篇 |
2010年 | 77篇 |
2009年 | 92篇 |
2008年 | 73篇 |
2007年 | 95篇 |
2006年 | 76篇 |
2005年 | 65篇 |
2004年 | 55篇 |
2003年 | 53篇 |
2002年 | 50篇 |
2001年 | 40篇 |
2000年 | 36篇 |
1999年 | 22篇 |
1998年 | 29篇 |
1997年 | 30篇 |
1996年 | 9篇 |
1995年 | 19篇 |
1994年 | 19篇 |
1993年 | 15篇 |
1992年 | 22篇 |
1991年 | 21篇 |
1990年 | 18篇 |
1989年 | 22篇 |
1988年 | 25篇 |
1987年 | 20篇 |
1986年 | 7篇 |
1985年 | 15篇 |
1984年 | 42篇 |
1983年 | 53篇 |
1982年 | 42篇 |
1981年 | 43篇 |
1980年 | 29篇 |
1979年 | 29篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1974年 | 3篇 |
1971年 | 4篇 |
排序方式: 共有1853条查询结果,搜索用时 31 毫秒
71.
72.
Nitrogen-fixing root nodules of Alnus crispa var. mollis Fern. were studied by transmission electron microscopy and by freeze-etching technique. Ultrathin sectioning of septate vesicles of the actinomycetal endophyte showed an electron transparent zone, the so-called void area, between the vesicle cell wall and its encapsulation material. This void area was not observed in the freeze-etching replicas of cryoprotected nodular tissue. It is suggested that the void area is the result of the coming-off of the vesicle cell wall from the capsule and that its formation reflects difficulty in fixing the voluminous mature vesicle of the root nodule endophyte. 相似文献
73.
Neurotrophins and FGF2 contribute to formation of the cochlea, but their roles in cochlear nucleus development are unknown. The effects of these factors may differ in the cochlea and cochlear nucleus, which may influence each other's development. It is important to analyze the effects of these factors on cellular structures at well‐defined steps in the normal morphogenetic sequence. The present study used immunohistochemistry to localize factors in situ and to test hypotheses about their roles in an in vitro model. Specific antibody staining revealed that TrkC, the NT3 receptor, is present in neural precursors prior to embryonic day E11 until after birth. NT3 appeared in precursor cells during migration (E13–E15) and disappeared at birth. TrkC and NT3 occurred in the same structures, including growing axons, terminals, and their synaptic targets. Thus, NT3 tracks the migration routes and the morphogenetic sequences within a window defined by TrkC. In vitro, the cochlear nucleus anlage was explanted from E11 embryos. Cultures were divided into groups fed with defined medium, with or without FGF2, BDNF, and NT3 supplements, alone or in combinations, for 7 days. When neuroblasts migrated and differentiated, immunostaining was used for locating NT3 and TrkC in the morphogenetic sequence, bromodeoxyuridine for proliferation, and synaptic vesicle protein for synaptogenesis. By time‐lapse imaging and quantitative measures, the results support the hypothesis that FGF2 promotes proliferation and migration. NT3 interacts with FGF2 and BDNF to promote neurite outgrowth, fasciculation, and synapse formation. Factors and receptors localize to the structural sites undergoing critical changes. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 相似文献
74.
Sealed, inside-out human red cell membrane vesicles, prepared by a modified method of Steck (Steck T.L. (1974) in Methods in Membrane Biology (Korn, E.D., ed.), Vol 2, pp. 245–281, Plenum Press, New York), accomplish an ATP and Mg2+-dependent uphill calcium uptake with a reproducible maximum rate of 12–15 nmol/mg vesicle protein per min under physiological conditions. This maximum rate is increased by about 60–70% in the presence of a heatstable cytoplasmic activator protein (calmodulin) obtained from red cells. Calcium efflux from inside-out vesicles is smaller than 0.01 nmol/mg vesicle protein per min at intravesicular calcium concentrations between 0.1 and 20.0 mM.In the presence of Mg2+, active calcium uptake is supported by ATP, ITP, or UTP, but not by ADP, AMP, or p-nitrophenyl phosphate. The optimum pH for the process is 7.4–7.6, and the activation energy is 19–20 kcal/mol, irrespective of the presence or absence of calmodulin. Calcium uptake in inside-out vesicles is unaffected by ouabain or oligomycin, but blocked by low concentrations of lanthanum, ruthenium red, quercetin and phloretin. K+ and Na+, when compared to choline+ or Li+, significantly increase active calcium uptake. This stimulation by K+ and Na+ is independent of that by calmodulin.Concentrated red cell cytoplasm activates calcium uptake at low soluble protein:membrane protein ratios, while a ‘deactivation’ of the transport occurs at high cytoplasm: membrane protein ratios. A heat-labile cytoplasmic protein fraction antagonizing calmodulin activation, can be separated by DEAE-Sephadex chromatography. Based on these findings the regulation of active calcium transport in human red cells is discussed. 相似文献
75.
76.
The synapse is formed between a presynapse (which releases neurotransmitter) and the postsynapse (which transduces this chemical signal). Over the past decade, presynaptic dysfunction has emerged as a key mediator of a series of neurodevelopmental and neurodegenerative disorders. This special issue will highlight some of the important presynaptic molecules and mechanisms that are disrupted in these conditions and reveal potential routes for therapy. 相似文献
77.
Delong Meng Qianmei Yang Chase H Melick Brenden C Park TingSung Hsieh Adna Curukovic MiHyeon Jeong Junmei Zhang Nicholas G James Jenna L Jewell 《The EMBO journal》2021,40(12)
The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Amino acids promote mTORC1 lysosomal localization and subsequent activation. However, the subcellular location or interacting proteins of mTORC1 under amino acid‐deficient conditions is not completely understood. Here, we identify ADP‐ribosylation factor GTPase‐activating protein 1 (ArfGAP1) as a crucial regulator of mTORC1. ArfGAP1 interacts with mTORC1 in the absence of amino acids and inhibits mTORC1 lysosomal localization and activation. Mechanistically, the membrane curvature‐sensing amphipathic lipid packing sensor (ALPS) motifs that bind to vesicle membranes are crucial for ArfGAP1 to interact with and regulate mTORC1 activity. Importantly, ArfGAP1 represses cell growth through mTORC1 and is an independent prognostic factor for the overall survival of pancreatic cancer patients. Our study identifies ArfGAP1 as a critical regulator of mTORC1 that functions by preventing the lysosomal transport and activation of mTORC1, with potential for cancer therapeutics. 相似文献
78.
《Expert review of proteomics》2013,10(5):667-677
Meningococcal disease is a global problem. Multivalent (A, C, Y, W135) conjugate vaccines have been developed and licensed; however, an effective vaccine against serogroup B has not yet become available. Outer membrane vesicle (OMV) vaccines have been used to disrupt serogroup B epidemics and outbreaks. Postgenomic technologies have been useful in aiding the discovery of new protein vaccine candidates. Moreover, proteomic technologies enable large-scale identification of membrane and surface-associated proteins, and provide suitable methods to characterize and standardize the antigen composition of OMV-based vaccines. 相似文献
79.
Mathilde Chaineau Maria S. Ioannou Peter S. McPherson 《Traffic (Copenhagen, Denmark)》2013,14(11):1109-1117
Rabs are the largest family of small GTPases and are master regulators of membrane trafficking. Following activation by guanine‐nucleotide exchange factors (GEFs), each Rab binds a specific set of effector proteins that mediate the various downstream functions of that Rab. Then, with the help of GTPase‐activating proteins, the Rab converts GTP to GDP, terminating its function. There are over 60 Rabs in humans and only a subset has been analyzed in any detail. Recently, Rab35 has emerged as a key regulator of cargo recycling at endosomes, with an additional role in regulation of the actin cytoskeleton. Here, we will focus on the regulation of Rab35 activity by the connecdenn/DENND1 family of GEFs and the TBC1D10/EPI64 family of GTPase‐activating proteins. We will describe how analysis of these proteins, as well as a plethora of Rab35 effectors has provided insights into Rab35 function. Finally, we will describe how Rab35 provides a novel link between the Rab and Arf family of GTPases with implications for tumor formation and invasiveness . 相似文献
80.
《Cell cycle (Georgetown, Tex.)》2013,12(10):1948-1955
Checkpoint kinase 1 (Chk1) plays key roles in all currently defined cell cycle checkpoints, but its functions in mouse oocyte meiosis remain unclear. In this study, we report the expression, localization and functions of Chk1 in mouse oocyte meiosis. Chk1 was expressed from germinal vesicle (GV) to metaphase II (MII) stages and localized to the spindle from pro-metaphase I (pro-MI) to MII stages in mouse oocytes. Chk1 depletion facilitated the G2/M transition while Chk1 overexpression inhibited the G2/M transition as indicated by germinal vesicle breakdown (GVBD), through regulation of Cdh1 and Cyclin B1. Chk1 depletion did not affect meiotic cell cycle progression after GVBD, but its overexpression after GVBD activated the spindle assembly checkpoint and prevented homologous chromosome segregation, thus arresting oocytes at pro-MI or metaphase I (MI) stages. These results suggest that Chk1 is indispensable for prophase I arrest and functions in G2/M checkpoint regulation in meiotic oocytes. Moreover, Chk1 overexpression affects meiotic spindle assembly checkpoint regulation and thus chromosome segregation. 相似文献