全文获取类型
收费全文 | 323篇 |
免费 | 38篇 |
国内免费 | 32篇 |
出版年
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 8篇 |
2015年 | 16篇 |
2014年 | 20篇 |
2013年 | 12篇 |
2012年 | 24篇 |
2011年 | 30篇 |
2010年 | 19篇 |
2009年 | 15篇 |
2008年 | 20篇 |
2007年 | 23篇 |
2006年 | 10篇 |
2005年 | 18篇 |
2004年 | 10篇 |
2003年 | 8篇 |
2002年 | 13篇 |
2001年 | 3篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 9篇 |
1991年 | 2篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 6篇 |
1973年 | 3篇 |
排序方式: 共有393条查询结果,搜索用时 15 毫秒
1.
Dominique Dorin-Semblat Claudia Demarta-Gatsi Romain Hamelin Florence Armand Teresa Gil Carvalho Marc Moniatte Christian Doerig 《PloS one》2015,10(12)
Casein kinase 1 (CK1) is a pleiotropic protein kinase implicated in several fundamental processes of eukaryotic cell biology. Plasmodium falciparum encodes a single CK1 isoform, PfCK1, that is expressed at all stages of the parasite’s life cycle. We have previously shown that the pfck1 gene cannot be disrupted, but that the locus can be modified if no loss-of-function is incurred, suggesting an important role for this kinase in intra-erythrocytic asexual proliferation. Here, we report on the use of parasite lines expressing GFP- or His-tagged PfCK1 from the endogenous locus to investigate (i) the dynamics of PfCK1 localisation during the asexual cycle in red blood cells, and (ii) potential interactors of PfCK1, so as to gain insight into the involvement of the enzyme in specific cellular processes. Immunofluorescence analysis reveals a dynamic localisation of PfCK1, with evidence for a pool of the enzyme being directed to the membrane of the host erythrocyte in the early stages of infection, followed by a predominantly intra-parasite localisation in trophozoites and schizonts and association with micronemes in merozoites. Furthermore, we present strong evidence that a pool of enzymatically active PfCK1 is secreted into the culture supernatant, demonstrating that PfCK1 is an ectokinase. Our interactome experiments and ensuing kinase assays using recombinant PfCK1 to phosphorylate putative interactors in vitro suggest an involvement of PfCK1 in many cellular processes such as mRNA splicing, protein trafficking, ribosomal, and host cell invasion. 相似文献
2.
3.
Sylviane Olschwang Richard Fabre Pierre Laurent-Puig Anne Vassal Bernard Hamelin Yusuke Nakamura Gilles Thomas 《Human genetics》1992,88(6):658-660
Summary The EF5.44 locus is in close proximity to the chromosome 5 region to which the genetic defect responsible for familial adenomatous polyposis has been mapped. We have devised two oligonucleotides that promote the specific polymerase chain reaction (PCR) amplificiation of a 365-bp sequence in this region. Analysis by denaturing gradient gel electrophoresis of the resulting fragment has unravelled individual differences that could be identified as a single base pair change in aMnlI restriction site. This PCR assayable polymorphism increases the informativeness at this locus, and should be useful in the presymptomatic diagnosis of familial adenomatous polyposis. 相似文献
4.
Testicular expression of PC4 in the rat: molecular diversity of a novel germ cell-specific Kex2/subtilisin-like proprotein convertase. 总被引:13,自引:0,他引:13
N G Seidah R Day J Hamelin A Gaspar M W Collard M Chrétien 《Molecular endocrinology (Baltimore, Md.)》1992,6(10):1559-1570
The rat cDNA sequence of PC4 (rPC4), representing a new member of the Kex2/subtilisin-like proprotein convertases, demonstrated the presence of at least three rPC4 mRNAs resulting in the production of rPC4-A (654 amino acids), rPC4-B (619 amino acids), and rPC4-C (609 amino acids) with different C-terminal sequences. Analogous to rat PC4, three cDNAs were also found for the mouse PC4. The observed molecular diversity of PC4 mRNA possibly results from the differential splicing and/or exon skipping of the parent gene. PC4 mRNA, with a major form at 2.8 kilobases, was highly abundant in the rat testis but could not be detected by Northern analysis in any other tissues including the central nervous system and peripheral tissues. Testicular cell separation studies combined with Northern analysis indicate the high expression levels of PC4 in germ cells but not in Leydig, Sertoli, or peritubular cells. In situ hybridization histochemistry confirms the site of PC4 gene expression as the pachytene spermatocytes and the round spermatids but not in the elongating spermatids. We also demonstrate the colocalization of PC4 with proenkephalin in testicular germ cells by in situ hybridization. A study of the ontogeny of PC4 indicated that PC4 mRNA was first expressed postnatally between days 19 and 22, coinciding with the first stages of spermiogenesis. The stage-specific expression of PC4 in testis indicates its potential role in the developmental maturation of germ cells and that this convertase may play a specific physiological function in reproduction. 相似文献
5.
N.G. Seidah K.L. Hsi G. De Serres J. Rochemont J. Hamelin T. Antakly M. Cantin M. Chrétien 《Archives of biochemistry and biophysics》1983,225(2):525-534
The isolation and purification of a 21,000-Da (pI 4.9) novel protein from porcine anterior pituitary and whole human pituitary is described. Comparison of the NH2-terminal sequence of the first 77 and 81 residues of the human and porcine homologs shows only one conservative substitution at residue 12, namely an Ala for a Thr between these two species. Such high sequence homology is also reflected in their amino acid composition. A computer data-bank search using a mutation data matrix and comparison with 338,327 segments of proteins revealed that this substance should be classified as belonging to a new protein superfamily. Immunocytochemical staining, using an antibody produced against a synthetic fragment, revealed the presence of immunostainable material in the anterior and posterior lobe of the pituitary and in the supraoptic nucleus of the hypothalamus. No staining was observed in the intermediate lobe of the pituitary. Furthermore, purified neurointermediate lobe secretory granule preparations were also shown to contain this novel polypeptide. 相似文献
6.
7.
J Yelle G Lussier A Pramatarova C Hamelin 《Biology of the cell / under the auspices of the European Cell Biology Organization》1990,70(1-2):9-18
Dog embryo kidney cells transformed by the human cytomegalovirus (HCMV) were obtained after non-permissive infection or transfection with viral DNA digested by restriction endonuclease EcoR I. The transformed cells, growing rapidly and showing an unlimited division potential, could use medium with only 2% serum for growth, contained nuclear virus antigens, and formed small colonies (less than 0.2 mm) in agarose. From 40 mice inoculated with transformed canine cells, only one eventually developed a tumor. Results indicate that dog cells are immortalized but not tumorigenically transformed by the human cytomegalovirus. 相似文献
8.
9.
Evolutionary Relationship of the Ligand-Gated Ion Channels and the Avermectin-Sensitive,Glutamate-Gated Chloride Channels 总被引:4,自引:0,他引:4
Demetrios K. Vassilatis Keith O. Elliston Philip S. Paress Michel Hamelin Joseph P. Arena James M. Schaeffer Lex H.T. Van der Ploeg Doris F. Cully 《Journal of molecular evolution》1997,44(5):501-508
Two cDNAs, GluClα and GluClβ, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin
class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707–711, 1994). Expression studies in Xenopus oocytes showed that GluClα and GluClβ have pharmacological profiles distinct from the glutamate-gated cation channels as
well as the γ-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of
related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined
the nucleotide sequence of the GluClα and GluClβ genes. In an attempt to understand the evolutionary relationship of these
channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic
analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several
intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position.
Phylogenetic analyses indicate that GluClα and GluClβ form a monophyletic subbranch in the ligand-gated ion channel superfamily
and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties
similar to GluClα and GluClβ, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride
channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination
with the distinct pharmacological properties demonstrate that GluClα and GluClβ belong to a discrete ligand-gated ion channel
family that may represent genes orthologous to the vertebrate glycine channels.
Received: 30 September 1996 / Accepted: 15 November 1996 相似文献
10.
The genomic organization of two parasitic wasps was analyzed by DNA reassociation. Cot curves revealed a pattern with three types of components. A highly repetitive DNA, accounting for 15 to 25% of the genome, was identified as satellite DNA. The moderately repetitive DNA corresponds to 26 to 42% of the genome in both species, and shows large variations in complexity, repetitive frequency and a number of sub-components between males and females. These variations are seen as resulting from DNA amplification during somatic and sexual differentiation. Dot blot analyses show that such DNA amplifications concern several types of structural and regulatory genes. The presence of repeated mobile elements was studied by the Roninson method to compare the repeated sequence patterns of Diadromus pulchellus and Eupelmus vuilleti with those of Drosophila melanogaster. The occurrence and organization of mobile elements in these Hymenoptera differ from those of the neighboring order of Diptera. The repetitive and unique components define very large genomes (1 to 3 × 109 base pairs). The genomic organization in Parasitica appears to be an extreme drosophilan type. We propose that the germinal genome of these parasitic wasps is primarily composed of satellite DNA blocks and very long stretches of unique sequences, separated by a few repeated and/or variously deleted, interspersed elements of each mobile element family. 相似文献