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   242篇
  免费   24篇
  2022年   2篇
  2021年   3篇
  2020年   5篇
  2019年   2篇
  2018年   4篇
  2017年   3篇
  2016年   5篇
  2015年   11篇
  2014年   5篇
  2013年   13篇
  2012年   21篇
  2011年   17篇
  2010年   16篇
  2009年   17篇
  2008年   11篇
  2007年   20篇
  2006年   13篇
  2005年   13篇
  2004年   5篇
  2003年   13篇
  2002年   21篇
  2001年   1篇
  2000年   1篇
  1999年   6篇
  1998年   7篇
  1997年   1篇
  1996年   1篇
  1995年   5篇
  1994年   1篇
  1993年   1篇
  1992年   3篇
  1991年   1篇
  1990年   2篇
  1989年   2篇
  1987年   4篇
  1986年   1篇
  1985年   1篇
  1984年   7篇
  1979年   1篇
排序方式: 共有266条查询结果,搜索用时 15 毫秒
201.
The first 14 exons of the APC gene have been screened by the denaturation gradient gel electrophoresis method in 160 unrelated patients with familial adenomatous polyposis coli (APC) syndrome. Four polymorphic variants corresponding to silent mutations not associated with the disease phenotype were observed. Mutations predicted to alter the coding property of the APC gene were observed in 26 patients. All these mutations are expected to lead either to aberrant splicing, to synthesis of a truncated APC protein because of the emergence of a stop codon, or to a change in the translation reading frame. Single-base-pair substitutions were observed on 21 occasions. The most frequent mutation (eight cases) was a C-to-T change which exclusively occurred on the nontranscribed strand within a CG dinucleotide.  相似文献   
202.
Simultaneous isolation of two platelet membrane subfractions was achieved by centrifugation on 40 % sucrose from a 100.000g crude membrane fraction. Characterization of both types of membranes was carried out by different biochemical and immunological markers. Using a surface label, 3H Concanavaline A (3HCon A), a marker enzyme, phosphodiesterase, and lipid analysis, one of the fraction has been identified as external or plasma membranes, the other consists of intracellular membranes. Further two specific antibodies directed against external membrane antigens (LeKa and LgG L) react almost exclusively with the external membranes. Finally both kinds of membranes were able to uptake calcium but the affinity for this cation was higher for the internal than for the external membranes. This suggests that both membranes are implicated in the regulation of the cytoplasmic calcium concentration and that the internal membranes (dense tubular system) play the major part in this regulation.  相似文献   
203.
Several nucleotide triphosphates (NTPs) were tested as energy source for the Ca2+ uptake by human platelet membrane vesicles. The Ca2+ uptake by these membranes was driven by ATP, GTP, ITP, UTP and CTP. The steady-state level of accumulated Ca2+ was equal with the different NTPs. The highest uptake velocity was found with ATP, but about 40–80% of the velocity with ATP could be accomplished with the other nucleotides. The highest affinity was also found with ATP (Km apparent  15 μM). The liberation of Pi from the various NTPs was measured simultaneously with the Ca2+ uptake. The coupling ratio (moles of Ca2+ taken up/moles of Pi liberated) varied from 0.4 for ATP to 2.3 for UTP and was almost independent of the NTP concentration. The enzyme activity with ATP as substrate is strongly dependent on the Ca2+ concentration in contrast to the activity with GTP, ITP, UTP or CTP.  相似文献   
204.
205.
Résumé Cette étude vise à élargir les connaissances du potentiel toxique de la β-exotoxine deB. thuringiensis Berliner sur lesCulicidae et particulièrement surAedes aegypti (L.),Anopheles stephensi (Liston) etCulex pipiens (L.). La toxicité par ingestion de la β-exotoxine deB. thuringiensis H 1 à 1 mg/ml est totale, sur les adultes males et femelles. La sensibilité des stades larvaires est proportionnelle à la concentration. La descendance des adultes, issus de larves traitées à une dose sublétale, présente une sensibilité accrue à l'exotoxine. La β-exotoxine induit un effet retard sur les mues larvaires ainsi que des effets tératogènes à la nymphose.
Summary The β-exotoxine ofB. thuringiensis H 1 acts as a larvicide and as an adulticide when ingested at high concentrations byAedes aegypti L.,Anopheles stephensi Liston orCulex pipiens L. Sublethal concentrations of β-exotoxin induce a delay of larval moulting and teratological effects on larvae and pupae. After sublethal application of β-exotoxine to larval stage the next larval generation presents an enhanced sensibility to this toxin.
  相似文献   
206.
We report on Dutch and Iranian families with affected individuals who present with moderate to severe intellectual disability and additional phenotypes including progressive tremor, speech impairment, and behavioral problems in certain individuals. A combination of exome sequencing and homozygosity mapping revealed homozygous mutations c.484G>A (p.Gly162Arg) and c.1898C>G (p.Pro633Arg) in SLC6A17. SLC6A17 is predominantly expressed in the brain, encodes a synaptic vesicular transporter of neutral amino acids and glutamate, and plays an important role in the regulation of glutamatergic synapses. Prediction programs and 3D modeling suggest that the identified mutations are deleterious to protein function. To directly test the functional consequences, we investigated the neuronal subcellular localization of overexpressed wild-type and mutant variants in mouse primary hippocampal neuronal cells. Wild-type protein was present in soma, axons, dendrites, and dendritic spines. p.Pro633Arg altered SLC6A17 was found in soma and proximal dendrites but did not reach spines. p.Gly162Arg altered SLC6A17 showed a normal subcellular distribution but was associated with an abnormal neuronal morphology mainly characterized by the loss of dendritic spines. In summary, our genetic findings implicate homozygous SLC6A17 mutations in autosomal-recessive intellectual disability, and their pathogenic role is strengthened by genetic evidence and in silico and in vitro functional analyses.  相似文献   
207.
Chromatin organization is essential for coordinated gene expression, genome stability, and inheritance of epigenetic information. The main components involved in chromatin assembly are specific complexes such as Chromatin Assembly Factor 1 (CAF‐1) and Histone Regulator (HIR), which deposit histones in a DNA synthesis‐dependent or ‐independent manner, respectively. Here, we characterize the role of the plant orthologs Histone Regulator A (HIRA), Ubinuclein (UBN) and Calcineurin Binding protein 1 (CABIN1), which constitute the HIR complex. Arabidopsis loss‐of‐function mutants for the various subunits of the complex are viable, but hira mutants show reduced fertility. We show that loss of HIRA reduces extractable histone H3 protein levels and decreases nucleosome occupancy at both actively transcribed genes and heterochromatic regions. Concomitantly, HIRA contributes to maintenance of silencing of pericentromeric repeats and certain transposons. A genetic analysis based on crosses between mutants deficient in subunits of the CAF‐1 and HIR complexes showed that simultaneous loss of both the CAF‐1 and HIR histone H3 chaperone complexes severely affects plant survival, growth and reproductive development. Our results suggest that HIRA partially rescues impaired histone deposition in fas mutants to preserve nucleosome occupancy, implying plasticity in histone variant interaction and deposition.  相似文献   
208.
209.
Brain high-speed supernatants from various lower and higher vertebrates were subjected to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, electroblot on nitrocellulose membranes, and immunolabelling using an anti-glutamic acid decarboxylase (anti-GAD) antiserum prepared from rat antigen. Rat brain extracts showed two distinct immunolabelled bands (MW 59,000 and 62,000 daltons). The molecular weight of the native enzyme was 120,000 daltons. The immunoblot pattern was not affected by a 3-h incubation of the homogenate. In the substantia nigra, the decrease in the immunolabelling of both bands corresponded very closely to the decrease of GAD activity following lesioning of the striato-nigral pathway. Moreover, experiments with preadsorbed antiserum showed that both subunits have common antigenic determinants. The immunolabelling was consistently more intense over the lightest band. The autoradiography of immunoprecipitated rat brain GAD, iodinated prior to electrophoresis, revealed two radiolabelled bands corresponding to the two immunolabelled ones. Their radioactivity was found in a one-to-five ratio which closely paralleled their respective immunolabelling intensity. Thus, the two subunits recognized by the antiserum are not present in stoichiometric proportions in the rat brain high-speed supernatant. These findings suggest the existence of two homodimeric GAD with common antigenic determinants which are present in different amounts. Immunoprecipitation curves of brain GAD from rat, mouse, rabbit, monkey, human, quail, frog, and trout were similar, with a less than 10-fold maximum shift in affinity for GAD. GAD immunoblots from the various higher vertebrates showed a pattern similar to that obtained in rat.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
210.
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