全文获取类型
收费全文 | 2150篇 |
免费 | 175篇 |
国内免费 | 7篇 |
出版年
2023年 | 24篇 |
2022年 | 37篇 |
2021年 | 99篇 |
2020年 | 43篇 |
2019年 | 36篇 |
2018年 | 72篇 |
2017年 | 48篇 |
2016年 | 72篇 |
2015年 | 120篇 |
2014年 | 152篇 |
2013年 | 163篇 |
2012年 | 190篇 |
2011年 | 183篇 |
2010年 | 110篇 |
2009年 | 93篇 |
2008年 | 121篇 |
2007年 | 101篇 |
2006年 | 87篇 |
2005年 | 112篇 |
2004年 | 110篇 |
2003年 | 66篇 |
2002年 | 65篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 21篇 |
1998年 | 23篇 |
1997年 | 10篇 |
1996年 | 10篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1987年 | 12篇 |
1986年 | 10篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1981年 | 6篇 |
1979年 | 4篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1968年 | 5篇 |
1955年 | 2篇 |
排序方式: 共有2332条查询结果,搜索用时 109 毫秒
91.
92.
TALL-1/BAFF/BLyS was recently identified as a member of the tumor necrosis factor (TNF) ligand family. The crystal structure of the functional soluble TALL-1 (sTALL-1) has been determined at 3.0 A. sTALL-1 forms a virus-like assembly with 200 A diameter in the crystals, containing 60 sTALL-1 monomers. The cluster formation is mediated by a "flap" region of the sTALL-1 monomer. The virus-like assembly was also detected in solution using gel filtration and electron microscopy. Deletion of the flap region disrupted the formation of the virus-like assembly. The mutant sTALL-1 still bound its receptor but could not activate NF-kappaB and did not stimulate B lymphocyte proliferation. Finally, we found the virus-like cluster of sTALL-1 exists in physiological condition. We propose that this virus-like assembly of sTALL-1 is the functional unit for TALL-1 in vivo. 相似文献
93.
Myosin VIIa,harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle 总被引:14,自引:0,他引:14
Boëda B El-Amraoui A Bahloul A Goodyear R Daviet L Blanchard S Perfettini I Fath KR Shorte S Reiners J Houdusse A Legrain P Wolfrum U Richardson G Petit C 《The EMBO journal》2002,21(24):6689-6699
Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia. 相似文献
94.
An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype 总被引:55,自引:0,他引:55
Wigle JT Harvey N Detmar M Lagutina I Grosveld G Gunn MD Jackson DG Oliver G 《The EMBO journal》2002,21(7):1505-1513
The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene Prox1 is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In Prox1(-)(/-) embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild-type embryos, those of Prox1-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that Prox1 activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype. 相似文献
95.
96.
Analysis of the kefA2 mutation suggests that KefA is a cation-specific channel involved in osmotic adaptation in Escherichia coli 总被引:2,自引:0,他引:2
McLaggan D Jones MA Gouesbet G Levina N Lindey S Epstein W Booth IR 《Molecular microbiology》2002,43(2):521-536
Mechanosensitive channels play an essential role in the regulation of turgor pressure in bacteria. In Escherichia coli, there are multiple mechanosensitive channels that have been characterized genetically: MscL, YggB and KefA. In this report, we describe the cloning of the kefA gene, the organization of the KefA protein and the phenotype of a missense mutation, kefA, which affects the KefA mechanosensitive channel. The altered function of the channel is manifest through increased sensitivity to K+ during growth at low osmolarity and complete inhibition of growth in media containing high K+ concentrations (0.6 M) in the presence of betaine or proline. Growth in high Na+ medium (0.6 M NaCl plus 20 mM K+) is normal. Analysis of the cytoplasmic pools shows that the mutant cannot regulate the K+ content of the cytoplasm when grown in high K+ medium. However, regulation of pools of amino acids is essentially normal and the mutant can accumulate high pools of proline during growth inhibition. The mutant shows increased sensitivity to acid hypo-osmotic shock (transition from neutral to acid pH combined with a reduction in osmolarity). The data are consistent with abnormal regulation of KefA in the presence of high K+ concentrations and either betaine or proline. 相似文献
97.
Dishevelled 2 is essential for cardiac outflow tract development,somite segmentation and neural tube closure 总被引:14,自引:0,他引:14
Hamblet NS Lijam N Ruiz-Lozano P Wang J Yang Y Luo Z Mei L Chien KR Sussman DJ Wynshaw-Boris A 《Development (Cambridge, England)》2002,129(24):5827-5838
The murine dishevelled 2 (Dvl2) gene is an ortholog of the Drosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway. Dvl2-deficient mice were produced to determine the role of Dvl2 in mammalian development. Mice containing null mutations in Dvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2(-/-) mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, approximately 90% of Dvl2(-/-) mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1 and Dvl2. Somite differentiation markers used to analyze Dvl2(-/-) and Dvl1(-/-);Dvl2(-/-) mutant embryos revealed mildly aberrant expression of Uncx4.1, delta 1 and myogenin, suggesting defects in somite segmentation. Finally, 2-3% of Dvl2(-/-) embryos displayed thoracic spina bifida, while virtually all Dvl1/2 double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis, somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes. 相似文献
98.
Circadian rhythms are the endogenous oscillations, occurring with a periodicity of approximately twenty-four hours, in the biochemical and behavioral functions of organisms. In mammals, the phase and period of the rhythm are synchronized to the daily light-dark cycle by light input through the eye. Certain retinal degenerative diseases affecting the photoreceptor cells, both rods and cones, in the outer retina reveal that classical opsins (i.e., rhodopsin and color opsins located in these cells) are essential for vision, but are not required for circadian photoreception. The mammalian cryptochromes and melanopsin (and possibly other opsin family pigments) have been proposed as circadian photoreceptor pigments that exist in the inner retina. Genetic analysis indicates that the cryptochromes, which contain flavin and folate as the light-absorbing cofactors, are the primary circadian photoreceptors. The classical photoreceptors in the outer retina, and melanopsin or other minor opsins in the inner retina, may perform redundant functions in circadian rhythmicity. 相似文献
99.
IRT1, an Arabidopsis transporter essential for iron uptake from the soil and for plant growth 总被引:30,自引:0,他引:30
下载免费PDF全文
![点击此处可从《The Plant cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Vert G Grotz N Dédaldéchamp F Gaymard F Guerinot ML Briat JF Curie C 《The Plant cell》2002,14(6):1223-1233
Plants are the principal source of iron in most diets, yet iron availability often limits plant growth. In response to iron deficiency, Arabidopsis roots induce the expression of the divalent cation transporter IRT1. Here, we present genetic evidence that IRT1 is essential for the uptake of iron from the soil. An Arabidopsis knockout mutant in IRT1 is chlorotic and has a severe growth defect in soil, leading to death. This defect is rescued by the exogenous application of iron. The mutant plants do not take up iron and fail to accumulate other divalent cations in low-iron conditions. IRT1-green fluorescent protein fusion, transiently expressed in culture cells, localized to the plasma membrane. We also show, through promoter::beta-glucuronidase analysis and in situ hybridization, that IRT1 is expressed in the external cell layers of the root, specifically in response to iron starvation. These results clearly demonstrate that IRT1 is the major transporter responsible for high-affinity metal uptake under iron deficiency. 相似文献
100.
The SWI/SNF chromatin-remodeling factor stimulates repair by human excision nuclease in the mononucleosome core particle 总被引:5,自引:0,他引:5
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
To investigate the role of chromatin remodeling in nucleotide excision repair, we prepared mononucleosomes with a 200-bp duplex containing an acetylaminofluorene-guanine (AAF-G) adduct at a single site. DNase I footprinting revealed a well-phased nucleosome structure with the AAF-G adduct near the center of twofold symmetry of the nucleosome core. This mononucleosome substrate was used to examine the effect of the SWI/SNF remodeling complex on the activity of human excision nuclease reconstituted from six purified excision repair factors. We found that the three repair factors implicated in damage recognition, RPA, XPA, and XPC, stimulate the remodeling activity of SWI/SNF, which in turn stimulates the removal of the AAF-G adduct from the nucleosome core by the excision nuclease. This is the first demonstration of the stimulation of nucleotide excision repair of a lesion in the nucleosome core by a chromatin-remodeling factor and contrasts with the ACF remodeling factor, which stimulates the removal of lesions from internucleosomal linker regions but not from the nucleosome core. 相似文献