全文获取类型
收费全文 | 116篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 3篇 |
理论与方法论 | 1篇 |
现状及发展 | 32篇 |
研究方法 | 27篇 |
综合类 | 50篇 |
自然研究 | 4篇 |
出版年
2021年 | 1篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 4篇 |
2013年 | 6篇 |
2012年 | 16篇 |
2011年 | 19篇 |
2010年 | 5篇 |
2009年 | 1篇 |
2008年 | 10篇 |
2007年 | 12篇 |
2006年 | 6篇 |
2005年 | 8篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 7篇 |
1990年 | 2篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1963年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有117条查询结果,搜索用时 46 毫秒
81.
Ambra1 regulates autophagy and development of the nervous system 总被引:1,自引:0,他引:1
Fimia GM Stoykova A Romagnoli A Giunta L Di Bartolomeo S Nardacci R Corazzari M Fuoco C Ucar A Schwartz P Gruss P Piacentini M Chowdhury K Cecconi F 《Nature》2007,447(7148):1121-1125
Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized. Beclin1 (Becn1; coiled-coil, myosin-like BCL2-interacting protein) is a principal regulator in autophagosome formation, and its deficiency results in early embryonic lethality. Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy, as revealed by its overexpression and by RNA interference experiments in vitro. Notably, Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death. In addition to identifying a new and essential element regulating the autophagy programme, our results provide in vivo evidence supporting the existence of a complex interplay between autophagy, cell growth and cell death required for neural development in mammals. 相似文献
82.
83.
Niko P. Bretz Alexei V. Salnikov Claudia Perne Sascha Keller Xiaoli Wang Claudia T. Mierke Mina Fogel Natalie Erbe-Hofmann Thomas Schlange Gerhard Moldenhauer Peter Altevogt 《Cellular and molecular life sciences : CMLS》2012,69(22):3863-3879
CD24 is a glycosyl-phosphatidylinositol-anchored membrane protein that is frequently over-expressed in a variety of human carcinomas and is correlated with poor prognosis. In cancer cell lines, changes of CD24 expression can alter several cellular properties in vitro and tumor growth in vivo. However, little is known about how CD24 mediates these effects. Here we have analyzed the functional consequences of CD24 knock-down or over-expression in human cancer cell lines. Depletion of CD24 reduced cell proliferation and adhesion, enhanced apoptosis, and regulated the expression of various genes some of which were identified as STAT3 target genes. Loss of CD24 reduced STAT3 and FAK phosphorylation. Diminished STAT3 activity was confirmed by specific reporter assays. We found that reduced STAT3 activity after CD24 knock-down was accompanied by altered Src phosphorylation. Silencing of Src, similar to CD24, targeted the expression of prototype STAT3-regulated genes. Likewise, the over-expression of CD24 augmented Src-Y416 phosphorylation, the recruitment of Src into lipid rafts and the expression of STAT3-dependent target genes. An antibody to CD24 was effective in reducing tumor growth of A549 lung cancer and BxPC3 pancreatic cancer xenografts in mice. Antibody treatment affected the level of Src-phosphorylation in the tumor and altered the expression of STAT3 target genes. Our results provide evidence that CD24 regulates STAT3 and FAK activity and suggest an important role of Src in this process. Finally, the targeting of CD24 by antibodies could represent a novel route for tumor therapy. 相似文献
84.
85.
Formalised and Non-Formalised Methods in Resource Management—Knowledge and Social Learning in Participatory Processes: An Introduction 总被引:1,自引:1,他引:0
Jens Newig Helmut Haberl Claudia Pahl-Wostl Dale S. Rothman 《Systemic Practice and Action Research》2008,21(6):381-387
The participation of non-state actors in public decision-making and transdisciplinary research is increasingly regarded as
an effective means to cope with growing uncertainties and complexities in human–nature interactions. The management of natural
resources is expected to profit from a broader knowledge base and processes of social learning, thus allowing for potentially
more informed and creative decision-making. Communication is a key element of transmitting knowledge and fostering social
learning. This article introduces the special issue, which assembles contributions that discuss different methods, instruments,
tools, and models that have been developed in order to facilitate the transmission of information as well its selection and
aggregation. Each of the contributions is briefly reviewed. The approaches discussed here and in the individual papers aim
to foster learning in participatory processes. We argue that a key aspect is the degree to which methods are formalised. Formalisation
refers to the extent to which information is channelled in a certain way, leaving more or less scope for open communication.
Depending on the goals and context, more or less formalised methods can be employed. We conclude by highlighting the context-dependency
of participatory processes in natural resource management and indicate some directions for future research.
相似文献
Jens NewigEmail: |
86.
Schormair B Kemlink D Roeske D Eckstein G Xiong L Lichtner P Ripke S Trenkwalder C Zimprich A Stiasny-Kolster K Oertel W Bachmann CG Paulus W Högl B Frauscher B Gschliesser V Poewe W Peglau I Vodicka P Vávrová J Sonka K Nevsimalova S Montplaisir J Turecki G Rouleau G Gieger C Illig T Wichmann HE Holsboer F Müller-Myhsok B Meitinger T Winkelmann J 《Nature genetics》2008,40(8):946-948
We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.44; rs1975197, P(nominal/lambda corrected) = 5.81 x 10(-9), OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS. 相似文献
87.
Claudia Compagnucci Monica Nizzardo Stefania Corti Ginevra Zanni Enrico Bertini 《Cellular and molecular life sciences : CMLS》2014,71(9):1623-1639
Neurogenesis is the developmental process regulating cell proliferation of neural stem cells, determining their differentiation into glial and neuronal cells, and orchestrating their organization into finely regulated functional networks. Can this complex process be recapitulated in vitro using induced pluripotent stem cell (iPSC) technology? Can neurodevelopmental and neurodegenerative diseases be modeled using iPSCs? What is the potential of iPSC technology in neurobiology? What are the recent advances in the field of neurological diseases? Since the applications of iPSCs in neurobiology are based on the capacity to regulate in vitro differentiation of human iPSCs into different neuronal subtypes and glial cells, and the possibility of obtaining iPSC-derived neurons and glial cells is based on and hindered by our poor understanding of human embryonic development, we reviewed current knowledge on in vitro neural differentiation from a developmental and cellular biology perspective. We highlight the importance to further advance our understanding on the mechanisms controlling in vivo neurogenesis in order to efficiently guide neurogenesis in vitro for cell modeling and therapeutical applications of iPSCs technology. 相似文献
88.
Bocchinfuso G Bobone S Mazzuca C Palleschi A Stella L 《Cellular and molecular life sciences : CMLS》2011,68(13):2281-2301
Since their initial discovery, 30 years ago, antimicrobial peptides (AMPs) have been intensely investigated as a possible
solution to the increasing problem of drug-resistant bacteria. The interaction of antimicrobial peptides with the cellular
membrane of bacteria is the key step of their mechanism of action. Fluorescence spectroscopy can provide several structural
details on peptide–membrane systems, such as partition free energy, aggregation state, peptide position and orientation in
the bilayer, and the effects of the peptides on the membrane order. However, these “low-resolution” structural data are hardly
sufficient to define the structural requirements for the pore formation process. Molecular dynamics simulations, on the other
hand, provide atomic-level information on the structure and dynamics of the peptide–membrane system, but they need to be validated
experimentally. In this review we summarize the information that can be obtained by both approaches, highlighting their versatility
and complementarity, suggesting that their synergistic application could lead to a new level of insight into the mechanism
of membrane destabilization by AMPs. 相似文献
89.
Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions 总被引:10,自引:0,他引:10
Winkelmann J Schormair B Lichtner P Ripke S Xiong L Jalilzadeh S Fulda S Pütz B Eckstein G Hauk S Trenkwalder C Zimprich A Stiasny-Kolster K Oertel W Bachmann CG Paulus W Peglau I Eisensehr I Montplaisir J Turecki G Rouleau G Gieger C Illig T Wichmann HE Holsboer F Müller-Myhsok B Meitinger T 《Nature genetics》2007,39(8):1000-1006
90.