全文获取类型
收费全文 | 155篇 |
免费 | 4篇 |
国内免费 | 2篇 |
专业分类
系统科学 | 1篇 |
现状及发展 | 39篇 |
研究方法 | 20篇 |
综合类 | 100篇 |
自然研究 | 1篇 |
出版年
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 5篇 |
2013年 | 4篇 |
2012年 | 13篇 |
2011年 | 14篇 |
2010年 | 9篇 |
2009年 | 5篇 |
2008年 | 15篇 |
2007年 | 10篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 11篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1996年 | 3篇 |
1994年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有161条查询结果,搜索用时 15 毫秒
101.
Bennett JT Stickney HL Choi WY Ciruna B Talbot WS Schier AF 《Nature》2007,450(7167):E1-2; discussion E2-4
In fish and amphibians, the dorsal axis is specified by the asymmetric localization of maternally provided components of the Wnt signalling pathway. Gore et al. suggest that the Nodal signal Squint (Sqt) is required as a maternally provided dorsal determinant in zebrafish. Here we test their proposal and show that the maternal activities of sqt and the related Nodal gene cyclops (cyc) are not required for dorsoventral patterning. 相似文献
102.
Gharavi AG Kiryluk K Choi M Li Y Hou P Xie J Sanna-Cherchi S Men CJ Julian BA Wyatt RJ Novak J He JC Wang H Lv J Zhu L Wang W Wang Z Yasuno K Gunel M Mane S Umlauf S Tikhonova I Beerman I Savoldi S Magistroni R Ghiggeri GM Bodria M Lugani F Ravani P Ponticelli C Allegri L Boscutti G Frasca G Amore A Peruzzi L Coppo R Izzi C Viola BF Prati E Salvadori M Mignani R Gesualdo L Bertinetto F Mesiano P Amoroso A Scolari F Chen N Zhang H Lifton RP 《Nature genetics》2011,43(4):321-327
We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 × 10?2? and 4.84 × 10?? and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures. 相似文献
103.
Genetics of early mammalian folliculogenesis 总被引:1,自引:0,他引:1
Early ovarian folliculogenesis begins with the breakdown of germ cell clusters and formation of primordial follicles. Primordial
follicles are the smallest ovarian follicle units continuously recruited to grow into primary and more advanced ovarian follicles.
Genes expressed in the germ cells such as Figla, Nobox, Kit and Ntrk2, as well as genes expressed in the surrounding somatic cells such as Foxl2, Kitl and Ngf, play critical functions during early folliculogenesis. Transgenic mice continue to provide important insights into the genetic
pathways that regulate early mammalian folliculogenesis. Genes critical in early folliculogenesis are important determinants
of reproductive life span and represent candidate genes for human ovarian failure.
Received 25 August 2005; received after revision 18 October 2005; accepted 21 November 2005 相似文献
104.
105.
106.
Jonghee Han Sunmin Jung Jiyeon Jang Tae-In Kam Hyunwoo Choi Byung-Ju Kim Jihoon Nah Dong-Gyu Jo Toshiyuki Nakagawa Masaki Nishimura Yong-Keun Jung 《Cellular and molecular life sciences : CMLS》2014,71(13):2561-2576
The gamma (γ)-secretase holoenzyme is composed of four core proteins and cleaves APP to generate amyloid beta (Aβ), a key molecule that causes major neurotoxicity during the early stage of Alzheimer’s disease (AD). However, despite its important role in Aβ production, little is known about the regulation of γ-secretase. OCIAD2, a novel modulator of γ-secretase that stimulates Aβ production, and which was isolated from a genome-wide functional screen using cell-based assays and a cDNA library comprising 6,178 genes. Ectopic expression of OCIAD2 enhanced Aβ production, while reduction of OCIAD2 expression suppressed it. OCIAD2 expression facilitated the formation of an active γ-secretase complex and enhanced subcellular localization of the enzyme components to lipid rafts. OCIAD2 interacted with nicastrin to stimulate γ-secretase activity. OCIAD2 also increased the interaction of nicastrin with C99 and stimulated APP processing via γ-secretase activation, but did not affect Notch processing. In addition, a cell-permeable Tat-OCIAD2 peptide that interfered with the interaction of OCIAD2 with nicastrin interrupted the γ-secretase-mediated AICD production. Finally, OCIAD2 expression was significantly elevated in the brain of AD patients and PDAPP mice. This study identifies OCIAD2 as a selective activator of γ-secretase to increase Aβ generation. 相似文献
107.
α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation 总被引:1,自引:0,他引:1
Parkinson's disease is the second most common neurodegenerative disorder. Growing evidence indicates a causative role of misfolded forms of the protein α-synuclein in the pathogenesis of Parkinson's disease. Intraneuronal aggregates of α-synuclein occur in Lewy bodies and Lewy neurites, the cytopathological hallmarks of Parkinson's disease and related disorders called synucleinopathies. α-Synuclein has long been defined as a 'natively unfolded' monomer of about 14?kDa (ref. 6) that is believed to acquire α-helical secondary structure only upon binding to lipid vesicles. This concept derives from the widespread use of recombinant bacterial expression protocols for in vitro studies, and of overexpression, sample heating and/or denaturing gels for cell culture and tissue studies. In contrast, we report that endogenous α-synuclein isolated and analysed under non-denaturing conditions from neuronal and non-neuronal cell lines, brain tissue and living human cells occurs in large part as a folded tetramer of about 58?kDa. Several methods, including analytical ultracentrifugation, scanning transmission electron microscopy and in vitro cell crosslinking confirmed the occurrence of the tetramer. Native, cell-derived α-synuclein showed α-helical structure without lipid addition and had much greater lipid-binding capacity than the recombinant α-synuclein studied heretofore. Whereas recombinantly expressed monomers readily aggregated into amyloid-like fibrils in vitro, native human tetramers underwent little or no amyloid-like aggregation. On the basis of these findings, we propose that destabilization of the helically folded tetramer precedes α-synuclein misfolding and aggregation in Parkinson's disease and other human synucleinopathies, and that small molecules that stabilize the physiological tetramer could reduce α-synuclein pathogenicity. 相似文献
108.
109.
INTRODUCTIONFungal laccases (benzenediol:oxygen oxidoreductases, EC 1.10.3.2) are multicopper oxidases, capable of reducing oxygen to water and simultaneously involved in oxidation of aromatic hydrogen donors. These enzymes and very similar polyphenol oxidases can be used as free or immobilized type both in water or in some organic solvents for improving several biotechnological processes (Burton etal. 1995; Luterek etal. 1998; Milstein etal. 1993). Of possible applications, the enzyme i… 相似文献
110.