全文获取类型
收费全文 | 131篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
丛书文集 | 2篇 |
现状及发展 | 35篇 |
研究方法 | 24篇 |
综合类 | 66篇 |
自然研究 | 5篇 |
出版年
2021年 | 2篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 2篇 |
2015年 | 1篇 |
2014年 | 1篇 |
2013年 | 6篇 |
2012年 | 13篇 |
2011年 | 15篇 |
2010年 | 6篇 |
2008年 | 8篇 |
2007年 | 13篇 |
2006年 | 15篇 |
2005年 | 7篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 8篇 |
1999年 | 1篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1981年 | 3篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1959年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有132条查询结果,搜索用时 15 毫秒
81.
Sub1A is an ethylene-response-factor-like gene that confers submergence tolerance to rice 总被引:10,自引:0,他引:10
Xu K Xu X Fukao T Canlas P Maghirang-Rodriguez R Heuer S Ismail AM Bailey-Serres J Ronald PC Mackill DJ 《Nature》2006,442(7103):705-708
Most Oryza sativa cultivars die within a week of complete submergence--a major constraint to rice production in south and southeast Asia that causes annual losses of over US 1 billion dollars and affects disproportionately the poorest farmers in the world. A few cultivars, such as the O. sativa ssp. indica cultivar FR13A, are highly tolerant and survive up to two weeks of complete submergence owing to a major quantitative trait locus designated Submergence 1 (Sub1) near the centromere of chromosome 9 (refs 3, 4, 5-6). Here we describe the identification of a cluster of three genes at the Sub1 locus, encoding putative ethylene response factors. Two of these genes, Sub1B and Sub1C, are invariably present in the Sub1 region of all rice accessions analysed. In contrast, the presence of Sub1A is variable. A survey identified two alleles within those indica varieties that possess this gene: a tolerance-specific allele named Sub1A-1 and an intolerance-specific allele named Sub1A-2. Overexpression of Sub1A-1 in a submergence-intolerant O. sativa ssp. japonica conferred enhanced tolerance to the plants, downregulation of Sub1C and upregulation of Alcohol dehydrogenase 1 (Adh1), indicating that Sub1A-1 is a primary determinant of submergence tolerance. The FR13A Sub1 locus was introgressed into a widely grown Asian rice cultivar using marker-assisted selection. The new variety maintains the high yield and other agronomic properties of the recurrent parent and is tolerant to submergence. Cultivation of this variety is expected to provide protection against damaging floods and increase crop security for farmers. 相似文献
82.
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response 总被引:1,自引:0,他引:1
L Kruidenier CW Chung Z Cheng J Liddle K Che G Joberty M Bantscheff C Bountra A Bridges H Diallo D Eberhard S Hutchinson E Jones R Katso M Leveridge PK Mander J Mosley C Ramirez-Molina P Rowland CJ Schofield RJ Sheppard JE Smith C Swales R Tanner P Thomas A Tumber G Drewes U Oppermann DJ Patel K Lee DM Wilson 《Nature》2012,488(7411):404-408
83.
Stephanie Oertel Klaus Scholich Andreas Weigert Dominique Thomas Julia Schmetzer Sandra Trautmann Marthe-Susanna Wegner Heinfried H. Radeke Natalie Filmann Bernhard Brüne Gerd Geisslinger Irmgard Tegeder Sabine Grösch 《Cellular and molecular life sciences : CMLS》2017,74(16):3039-3055
Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease like ulcerative colitis. The molecular mechanisms are not well understood, but likely involve dysregulation of membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. Here, we used a loss-of-function model (CerS2+/+ and CerS2?/? mice) to investigate the impact of ceramide synthase 2, a key enzyme in the generation of very long-chain ceramides, in the dextran sodium salt (DSS) evoked model of UC. CerS2?/? mice developed more severe disease than CerS2+/+ mice in acute DSS and chronic AOM/DSS colitis. Deletion of CerS2 strongly reduced very long-chain ceramides (Cer24:0, 24:1) but concomitantly increased long-chain ceramides and sphinganine in plasma and colon tissue. In naive CerS2?/? mice, the expression of tight junction proteins including ZO-1 was almost completely lost in the colon epithelium, leading to increased membrane permeability. This could also be observed in vitro in CerS2 depleted Caco-2 cells. The increase in membrane permeability in CerS2?/? mice did not manifest with apparent clinical symptoms in naive mice, but with slight inflammatory signs such as an increase in monocytes and IL-10. AOM/DSS and DSS treatment alone led to a further deterioration of membrane integrity and to severe clinical symptoms of the disease. This was associated with stronger upregulation of cytokines in CerS2?/? mice and increased infiltration of the colon wall by immune cells, particularly monocytes, CD4+ and Th17+ T-cells, and an increase in tumor burden. In conclusion, CerS2 is crucial for the maintenance of colon barrier function and epithelial integrity. CerS2 knockdown, and associated changes in several sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon, may weaken endogenous defense against the endogenous microbiome. 相似文献
84.
85.
Roell W Lewalter T Sasse P Tallini YN Choi BR Breitbach M Doran R Becher UM Hwang SM Bostani T von Maltzahn J Hofmann A Reining S Eiberger B Gabris B Pfeifer A Welz A Willecke K Salama G Schrickel JW Kotlikoff MI Fleischmann BK 《Nature》2007,450(7171):819-824
Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy. 相似文献
86.
Caitlin Collin Frank Hauser Ernesto Gonzalez de Valdivia Shizhong Li Julia Reisenberger Eva M. M. Carlsen Zaid Khan Niels Ø. Hansen Florian Puhm Leif Søndergaard Justyna Niemiec Magdalena Heninger Guilin R. Ren Cornelis J. P. Grimmelikhuijzen 《Cellular and molecular life sciences : CMLS》2013,70(21):4197-4197
87.
88.
89.
Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo 总被引:73,自引:0,他引:73
Walsh DM Klyubin I Fadeeva JV Cullen WK Anwyl R Wolfe MS Rowan MJ Selkoe DJ 《Nature》2002,416(6880):535-539
Although extensive data support a central pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, the amyloid hypothesis remains controversial, in part because a specific neurotoxic species of Abeta and the nature of its effects on synaptic function have not been defined in vivo. Here we report that natural oligomers of human Abeta are formed soon after generation of the peptide within specific intracellular vesicles and are subsequently secreted from the cell. Cerebral microinjection of cell medium containing these oligomers and abundant Abeta monomers but no amyloid fibrils markedly inhibited hippocampal long-term potentiation (LTP) in rats in vivo. Immunodepletion from the medium of all Abeta species completely abrogated this effect. Pretreatment of the medium with insulin-degrading enzyme, which degrades Abeta monomers but not oligomers, did not prevent the inhibition of LTP. Therefore, Abeta oligomers, in the absence of monomers and amyloid fibrils, disrupted synaptic plasticity in vivo at concentrations found in human brain and cerebrospinal fluid. Finally, treatment of cells with gamma-secretase inhibitors prevented oligomer formation at doses that allowed appreciable monomer production, and such medium no longer disrupted LTP, indicating that synaptotoxic Abeta oligomers can be targeted therapeutically. 相似文献
90.
Rac GTPases control axon growth, guidance and branching 总被引:14,自引:0,他引:14
Ng J Nardine T Harms M Tzu J Goldstein A Sun Y Dietzl G Dickson BJ Luo L 《Nature》2002,416(6879):442-447
Growth, guidance and branching of axons are all essential processes for the precise wiring of the nervous system. Rho family GTPases transduce extracellular signals to regulate the actin cytoskeleton. In particular, Rac has been implicated in axon growth and guidance. Here we analyse the loss-of-function phenotypes of three Rac GTPases in Drosophila mushroom body neurons. We show that progressive loss of combined Rac1, Rac2 and Mtl activity leads first to defects in axon branching, then guidance, and finally growth. Expression of a Rac1 effector domain mutant that does not bind Pak rescues growth, partially rescues guidance, but does not rescue branching defects of Rac mutant neurons. Mosaic analysis reveals both cell autonomous and non-autonomous functions for Rac GTPases, the latter manifesting itself as a strong community effect in axon guidance and branching. These results demonstrate the central role of Rac GTPases in multiple aspects of axon development in vivo, and suggest that axon growth, guidance and branching could be controlled by differential activation of Rac signalling pathways. 相似文献