首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   549篇
  免费   59篇
  2022年   7篇
  2021年   18篇
  2020年   7篇
  2019年   7篇
  2018年   14篇
  2016年   9篇
  2015年   21篇
  2014年   21篇
  2013年   25篇
  2012年   48篇
  2011年   29篇
  2010年   11篇
  2009年   21篇
  2008年   16篇
  2007年   11篇
  2006年   20篇
  2005年   11篇
  2004年   11篇
  2003年   12篇
  2002年   15篇
  2001年   12篇
  2000年   8篇
  1999年   10篇
  1998年   11篇
  1997年   5篇
  1996年   6篇
  1995年   5篇
  1993年   9篇
  1992年   9篇
  1991年   12篇
  1990年   9篇
  1989年   11篇
  1988年   5篇
  1987年   14篇
  1985年   11篇
  1984年   7篇
  1983年   8篇
  1982年   6篇
  1980年   5篇
  1979年   6篇
  1978年   7篇
  1974年   11篇
  1973年   4篇
  1972年   4篇
  1971年   10篇
  1970年   6篇
  1969年   5篇
  1968年   4篇
  1966年   9篇
  1965年   4篇
排序方式: 共有608条查询结果,搜索用时 15 毫秒
81.
82.
Proteinase A, a yeast aspartyl protease that is highly homologous to the mammalian lysosomal aspartyl protease, cathepsin D, was expressed in Xenopus oocytes and its biosynthesis and post-translational modifications were characterized. While 29-45% of the proteinase A was secreted from oocytes, approximately 37% of the cell-associated proteinase A underwent proteolytic cleavage, characteristic of delivery to a lysosomal organelle. Although proteinase A is not targeted to the yeast vacuole by a mannose 6-phosphate receptor-dependent pathway, 2-5% of the proteinase A molecules expressed in oocytes bound to a Man-6-P receptor column. However, analysis of its [2-3H]mannose-labeled oligosaccharides revealed that 14-23% of these units contain phosphomannosyl residues. A hybrid molecule (H6), in which the propiece and first 12 amino acids of proteinase A were changed to the cathepsin D sequence, was also expressed in oocytes. The binding of H6 to the Man-6-P receptor was approximately 12-fold greater than observed for proteinase A. This increased level of receptor binding could be accounted for by three factors: 1) a small increase in the total amount of phosphorylated oligosaccharides, 2) an increase in the number of oligosaccharides which acquire two phosphomonoesters, and 3) the presence of a greater percentage of oligosaccharides with one phosphomonoester which exhibit high affinity binding to the Man-6-P receptor. These results demonstrate that proteinase A is recognized by UDP-GlcNAc:lysosomal enzyme N-acetylglucosaminylphosphotransferase. However, this interaction is altered by the addition of cathepsin D sequences, resulting in the generation of a higher affinity ligand for binding to the Man-6-P receptor.  相似文献   
83.
We report a simple type of reciprocal chromosomal translocation in the LOU rat IgE-secreting immunocytoma cell line, IR162, involving the c-myc protooncogene and the switch region of the epsilon immunoglobulin heavy chain, c-myc/S epsilon. By cloning and sequencing the translocation-associated and the homologous normal c-myc and S epsilon DNAs, we have identified the position of the translocational junction in both the c-myc 5'-flanking region and the repetitive elements of the S epsilon region. The translocational recombination was precise, and no insertion or N-addition was found in the junctional region, leaving all the c-myc exons, together with two promoter sites, intact. RNase mapping confirmed that the same promoters were utilized in IR162 and normal LOU spleen cells. No point mutation was found in the 5'-flanking region and the 3'-portion of exon 1 of the translocated c-myc gene. However, the putative silencer region was lost with the translocation. It was also noticed that a strikingly AT-rich sequence associated with S epsilon region had translocated to the 5'-flanking region of c-myc gene. We discuss the possibility that a change of DNA topology, perhaps either due to the juxtaposition of an AT-rich sequence of the S epsilon region, or to the loss of the putative silencer element, may contribute to c-myc gene deregulation in IR162.  相似文献   
84.
85.
C J Faust  G E Herman 《Genomics》1991,11(1):154-164
Using pulsed-field gel electrophoresis, a 3 million-bp physical map containing the X-linked loci Gabra3, DXPas8, CamL1, and Rsvp has been constructed for a segment of the mouse X chromosome homologous to human Xq28. Detailed mapping was performed using single and double digestions with rare-cutter restriction enzymes. Gabra3 and DXPas8 have been shown to be physically linked within a maximal distance of 1600 kb, DXPas8 and CamL1 within 750 kb, and CamL1 and Rsvp within 450 kb. In addition, several CpG islands have been detected in the region encompassing CamL1 and Rsvp. These studies confirm a gene order of cen-Gabra3-DXPas8-CamL1-Rsvp-tel determined by genetic mapping in interspecific backcrosses (A.S. Ryder-Cook et al., 1988, EMBO J. 7: 3017-3021; G.E. Herman et al., 1991, Genomics 9: 670-677). Physical distances for the loci studied agree with the calculated genetic distances. Assuming that there is conserved linkage between man and mouse in the region, the physical mapping data presented here may help to clarify the uncertain gene order for some human Xq28 loci.  相似文献   
86.
87.
At least three different subcellular compartments, including peroxisomes, are involved in cholesterol biosynthesis. Because proper CNS development depends on de novo cholesterol biosynthesis, peroxisomes must play a critical functional role in this process. Surprisingly, no information is available on the peroxisomal isoprenoid/cholesterol biosynthesis pathway in normal brain tissue or on the compartmentalization of isoprene metabolism in the CNS. This has been due mainly to the lack of a well-defined isolation procedure for brain tissue, and also to the presence of myelin in brain tissue, which results in significant contamination of subcellular fractions. As a first step in characterizing the peroxisomal isoprenoid pathway in the CNS, we have established a purification procedure to isolate peroxisomes and other cellular organelles from the brain stem, cerebellum and spinal cord of the mouse brain. We demonstrate by use of marker enzymes and immunoblotting with antibodies against organelle specific proteins that the isolated peroxisomes are highly purified and well separated from the ER and mitochondria, and are free of myelin contamination. The isolated peroxisomal fraction was purified at least 40-fold over the original homogenate. In addition, we show by analytical subcellular fractionation and immunoelectron microscopy that HMG-CoA reductase protein and activity are localized both in the ER and peroxisomes in the CNS.  相似文献   
88.
Summary: Mouse embryos homozygous for the allele eedl7Rn5‐3354SB of the Polycomb Group gene embryonic ectoderm development (eed) display a gastrulation defect in which epiblast cells move through the streak and form extraembryonic mesoderm derivatives at the expense of development of the embryo proper. Here we demonstrate that homozygous mutant ES cells have the capacity to differentiate embryonic cell types both in vitro as embryoid bodies and in vivo as chimeric embryos. In chimeric embryos, eed mutant cells can respond to wild‐type signals and participate in normal gastrulation movements. These results indicate a non–cell‐autonomous function for eed. Evidence of mutant cell exclusion from the forebrain and segregation within somites, however, suggests that eed has cell‐autonomous roles in aspects of organogenesis. A requirement for eed in the epiblast during embryonic development is supported by the fact that high‐contribution chimeras could not be rescued by a wild‐type extraembryonic environment. genesis 31:142–146, 2001. © 2001 Wiley‐Liss, Inc.  相似文献   
89.
90.
The secretory granule protein syncollin was first identified in the exocrine pancreas where a population of the protein is associated with the luminal surface of the zymogen granule membrane. In this study we provide first morphological and biochemical evidence that, in addition to its pancreatic localization, syncollin is also present in neutrophilic granulocytes of rat and human origin. By immunohistological studies, syncollin was detected in neutrophilic granulocytes of the spleen. Furthermore, syncollin is expressed by the promyelocytic HL-60 cells, where it is stored in azurophilic granules and in a vesicular compartment. These findings were confirmed by fractionation experiments and immunoelectron microscopy. Treatment with a phorbol ester triggered the release of syncollin indicating that in HL-60 cells it is a secretory protein that can be mobilized upon stimulation. A putative role for syncollin in host defense is discussed.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号