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   489篇
  免费   44篇
  国内免费   3篇
  2021年   5篇
  2019年   2篇
  2018年   7篇
  2017年   6篇
  2016年   8篇
  2015年   29篇
  2014年   15篇
  2013年   27篇
  2012年   36篇
  2011年   24篇
  2010年   27篇
  2009年   19篇
  2008年   22篇
  2007年   28篇
  2006年   24篇
  2005年   22篇
  2004年   13篇
  2003年   16篇
  2002年   13篇
  2001年   14篇
  2000年   10篇
  1999年   8篇
  1998年   12篇
  1997年   7篇
  1996年   5篇
  1995年   6篇
  1994年   7篇
  1993年   3篇
  1992年   9篇
  1991年   8篇
  1990年   11篇
  1989年   4篇
  1988年   5篇
  1987年   8篇
  1986年   6篇
  1985年   8篇
  1983年   3篇
  1981年   2篇
  1980年   2篇
  1979年   10篇
  1978年   2篇
  1977年   7篇
  1974年   3篇
  1973年   3篇
  1972年   5篇
  1971年   4篇
  1970年   2篇
  1969年   4篇
  1968年   2篇
  1967年   3篇
排序方式: 共有536条查询结果,搜索用时 15 毫秒
31.
Nicastrin is a component of the gamma-secretase complex that has been shown to adhere to presenilin-1 (PS1), Notch, and APP. Here we demonstrate that Nicastrin-deficient mice showed a phenotype that is indistinguishable from PS1/PS2 double knock-out mice, whereas heterozygotes were healthy and viable. Fibroblasts derived from Nicastrin-deficient embryos were unable to generate amyloid beta-peptide and failed to release the intracellular domain of APP- or Notch1-Gal4-VP16 fusion proteins. Additionally, C- and N-terminal fragments of PS1 and the C-terminal fragments of PS2 were not detectable in Nicastrin-null fibroblasts, whereas full-length PS1 accumulated in null fibroblasts, indicating that Nicastrin is required for the endoproteolytic processing of presenilins. Interestingly, cells derived from Nicastrin heterozygotes produced relatively higher levels of amyloid beta-peptide whether the source was endogenous mouse or transfected human APP. These data demonstrate that Nicastrin is essential for the gamma-secretase cleavage of APP and Notch in mammalian cells and that Nicastrin has both positive and negative functions in the regulation of gamma-secretase activity.  相似文献   
32.
The Ccs1 gene, encoding a highly divergent novel component of a system II type c-type cytochrome biogenesis pathway, is encoded by the previously defined CCS1 locus in Chlamydomonas reinhardtii. phoA and lacZalpha bacterial topological reporters were used to deduce a topological model of the Synechocystis sp. 6803 Ccs1 homologue, CcsB. CcsB, and therefore by analogy Ccs1, possesses a large soluble lumenal domain at its C terminus that is tethered in the thylakoid membrane by three closely spaced transmembrane domains in the N-terminal portion of the protein. Molecular analysis of ccs1 alleles reveals that the entire C-terminal soluble domain is essential for Ccs1 function and that a stromal loop appears to be important in vivo, at least for maintenance of Ccs1. Site-directed mutational analysis reveals that a single histidine (His(274)) within the last transmembrane domain, preceding the large lumenal domain, is required for c-type cytochrome assembly, whereas an invariant cysteine residue (Cys(199)) is shown to be non-essential. Ccs1 is proposed to interact with other Ccs components based on its reduced accumulation in ccs2, ccs3, ccs4, and ccsA strains.  相似文献   
33.
About 25% of humans with chronic gastritis are negative for Helicobacter pylori, suggesting that other bacteria are capable of causing inflammation. Bacterial overgrowth may occur in the stomach under conditions of reduced acid secretion. In this review, we will explore what is generally known about non-H. pylori organisms and their ability to induce gastritis, with particular focus on Acinetobacter lwoffi.  相似文献   
34.
Myocardial iron deficiency complicates chronic intrauterine hypoxemia during diabetic pregnancies. To understand the effect of both conditions during fetal life on intracardiac iron prioritization, we measured heart myoglobin, cytochrome c, and elemental iron concentrations in six iron-deficient, hypoxic, five iron-sufficient, hypoxic, six iron-deficient, normoxic, and six iron-sufficient, normoxic newborn guinea pigs. The iron-deficient, hypoxic group had lower heart iron (p = 0.03) but higher myoglobin concentration (p < 0.0001) when compared with the iron-sufficient, normoxic group. The percentage of iron incorporated into myoglobin was higher than control in the iron-deficient, hypoxic group (23.2+/-7.2% vs. 5.2+/-0.8%; p < 0.001) and increased as total heart iron decreased (r = 0.97; p < 0.001). In contrast, heart cytochrome c concentration was lower than control in the iron-deficient, hypoxic group (p = 0.01), with equal percentages of heart iron incorporated into cytochrome c. This intracellular prioritization of myocardial iron to myoglobin and away from cytochrome c following combined fetal hypoxemia and iron deficiency may represent an adaptive mechanism to preserve myocardial tissue oxygenation, although at the expense of oxidative phosphorylative capability.  相似文献   
35.
Acharya  S; Rayborn  ME; Hollyfield  JG 《Glycobiology》1998,8(10):997-1006
Rod and cone photoreceptors project from the outer retinal surface into a carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM glycoconjugates are distributed around rods and cones. Wheat germ agglutinin (WGA) strongly decorates the rod matrix domains and weakly decorates the cone matrix domains. This study characterizes the major WGA-binding glycoprotein in the human IPM, which we refer to as SPACR (sialoprotein associated with cones and rods). SPACR, which has a molecular weight of 147 kDa, was isolated and purified from the IPM by lectin affinity chromatography. A polyclonal antibody to SPACR was prepared that colocalizes in tissue preparations with WGA-binding domains in the IPM. Sequential digestion of SPACR with N- and O- glycosidases results in a systematic increase in electrophorectic mobility, indicating the presence of both N- and O-linked glycoconjugates. Complete deglycosylation results in a reduction in the relative molecular mass of SPACR by about 30%. Analysis of lectin binding allowed us to identify some of the structural characteristics of SPACR glycoconjugates. Treatment with neuraminidase exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA), specific for alpha2-6 linked sialic acid, does not, indicating that the dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate, NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR suggests that this glycoprotein may contribute substantially to the polyanionic nature of the IPM. The carbohydrate chains present on SPACR could also provide sites for extensive crosslinking and participate in the formation of the ordered IPM lattice that surrounds the elongate photoreceptors projecting from the outer retinal surface.   相似文献   
36.
Aim  Increasing aridity over geological time-scales has driven a high degree of speciation within the Eucalyptus group in Australia. Isolation of gene pools by climatic and edaphic conditions and high rates of out-crossing have given rise to a large diversity of adaptive traits. Among these traits, adaptations of cellular biochemistry are likely to be significant in preserving cellular function during arid conditions. The aim of this study was to determine the quantitative and qualitative distribution of soluble carbohydrates and polyols in Eucalyptus .
Location  Australia.
Methods  We sampled 279 of the 700+ documented eucalypts (in the three genera comprising the eucalypts: Angophora Cav., Corymbia Hill & Johnson and Eucalyptus L'Hér.) and analysed leaf tissues for the occurrence of low-molecular-weight carbohydrates and polyols.
Results  We have uncovered a discrete pattern in concentration of quercitol (a cyclitol) that correlates strongly with the current taxonomic classification based on both morphology and DNA sequencing. We also uncovered a further and stronger correlation between the presence of quercitol in leaf tissues and a reduced growth (mallee) form.
Main conclusions  These findings, together with the chemical properties of quercitol, suggest that we have uncovered a chemical marker of structural adaptations to arid conditions, thus providing a putative, broad-scale functional link to adaptation to aridity.  相似文献   
37.
To investigate the impact of iron deficiency on bioenergetic pathways in Chlamydomonas, we compared growth rates, iron content, and photosynthetic parameters systematically in acetate versus CO2-grown cells. Acetate-grown cells have, predictably (2-fold) greater abundance of respiration components but also, counter-intuitively, more chlorophyll on a per cell basis. We found that phototrophic cells are less impacted by iron deficiency and this correlates with their higher iron content on a per cell basis, suggesting a greater capacity/ability for iron assimilation in this metabolic state. Phototrophic cells maintain both photosynthetic and respiratory function and their associated Fe-containing proteins in conditions where heterotrophic cells lose photosynthetic capacity and have reduced oxygen evolution activity. Maintenance of NPQ capacity might contribute to protection of the photosynthetic apparatus in iron-limited phototrophic cells. Acetate-grown iron-limited cells maintain high growth rates by suppressing photosynthesis but increasing instead respiration. These cells are also able to maintain a reduced plastoquinone pool.  相似文献   
38.
Chlamydomonas reinhardtii, a unicellular green alga, has been exploited as a reference organism for identifying proteins and activities associated with the photosynthetic apparatus and the functioning of chloroplasts. Recently, the full genome sequence of Chlamydomonas was generated and a set of gene models, representing all genes on the genome, was developed. Using these gene models, and gene models developed for the genomes of other organisms, a phylogenomic, comparative analysis was performed to identify proteins encoded on the Chlamydomonas genome which were likely involved in chloroplast functions (or specifically associated with the green algal lineage); this set of proteins has been designated the GreenCut. Further analyses of those GreenCut proteins with uncharacterized functions and the generation of mutant strains aberrant for these proteins are beginning to unmask new layers of functionality/regulation that are integrated into the workings of the photosynthetic apparatus.  相似文献   
39.
每搏量变异度是动态的容量监测指标.机械通气患者心肺的相互作用是每搏量变异度的产生基础,通过动脉压力波形分析技术可以进行连续监测.每搏量变异度能够准确预测容量治疗反应,与静态的血流动力学参数相比,对于优化心输出量和组织氧供更有优势,但也存在一定的局限性.每搏量变异度受多种因素影响且不能用于自主呼吸和心律失常的患者.临床应用时应该综合考虑其影响因素,结合其他的指标和方法指导容量治疗.  相似文献   
40.
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