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排序方式: 共有342条查询结果,搜索用时 31 毫秒
21.
Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at the plasma membrane
Sassan Hafizi Anna Gustafsson Cecilia Oslakovic Anders Tengholm Bruno O. Villoutreix 《Biochemical and biophysical research communications》2010,399(3):396-1844
Tensins are proposed cytoskeleton-regulating proteins. However, Tensin2 additionally inhibits Akt signalling and cell survival. Structural modelling of the Tensin2 phosphatase (PTPase) domain revealed an active site-like pocket receptive towards phosphoinositides. Tensin2-expressing HEK293 cells displayed negligible levels of plasma membrane phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) under confocal microscopy. However, mock-transfected cells, and Tensin2 cells harbouring a putative phosphatase-inactivating mutation, exhibited significant PtdIns(3,4,5)P3 levels, which decreased upon phosphatidylinositol 3-kinase inhibition with LY294002. In contrast, wtTensin3, mock and mutant cells were identical in membrane PtdIns(3,4,5)P3 and Akt phosphorylation. In vitro lipid PTPase activity was however undetectable in isolated recombinant PTPase domains of both Tensins, indicating a possible loss of structural stability when expressed in isolation. In summary, we provide evidence that Tensin2, in addition to regulating cytoskeletal dynamics, influences phosphoinositide-Akt signalling through its PTPase domain. 相似文献
22.
外源突变基因AGM3过表达对烟草开花的抑制和花器官发育的影响 总被引:1,自引:0,他引:1
为了解AGM3基因在异源植物中对开花及花器官发育的影响,采用农杆菌介导法将dominant negative mutation(DNM)结构基因35S-AGM3-E9导入烟草(Nicotiana tabacum),经PCR和Southern检测获得了一批阳性转化植株.荧光定量分析结果显示,AGM3在各个转基因株系中均有... 相似文献
23.
The anticoagulant protein C pathway 总被引:16,自引:0,他引:16
The anticoagulant protein C system regulates the activity of coagulation factors VIIIa and Va, cofactors in the activation of factor X and prothrombin, respectively. Protein C is activated on endothelium by the thrombin-thrombomodulin-EPCR (endothelial protein C receptor) complex. Activated protein C (APC)-mediated cleavages of factors VIIIa and Va occur on negatively charged phospholipid membranes and involve protein cofactors, protein S and factor V. APC also has anti-inflammatory and anti-apoptotic activities that involve binding of APC to EPCR and cleavage of PAR-1 (protease-activated receptor-1). Genetic defects affecting the protein C system are the most common risk factors of venous thrombosis. The protein C system contains multi-domain proteins, the molecular recognition of which will be reviewed. 相似文献
24.
Sørensen KW Nicolaes GA Villoutreix BO Yamazaki T Tans G Rosing J Dahlbäck B 《Biochemistry》2004,43(19):5803-5810
Activated coagulation factor V (FVa) is a cofactor of activated factor X (FXa) in prothrombin activation. FVa is composed of a light chain (LC) and a heavy chain (HC) that are noncovalently associated in a calcium-dependent manner. We constructed a recombinant FV Asp111Asn/Asp112Asn mutant (rFV-NN) to abolish calcium binding to a potential calcium-binding site in FVa in order to study the specific role of these residues in the expression of FVa activity. Whereas thrombin-activated recombinant FV wild type (rFV-wt) presented with stable FVa activity, incubation of rFV-NN with thrombin resulted in a temporary increase in FVa activity, which was rapidly lost upon prolonged incubation. Loss of FVa activity was most likely due to dissociation of HC and LC since, upon chromatography of rFVa-NN on a SP-Sepharose column, the HC did not bind significantly to the resin whereas the LC bound and could be eluted at high ionic strength. In contrast, rFVa-wt adhered to the column, and both the HC and LC coeluted at high ionic strength. In the presence of phospholipid vesicles, the loss of rFVa-NN activity was partially prevented by FXa, active site inhibited FXa, and prothombin in a dose-dependent manner. We conclude that the introduced amino acid substitutions result in a loss of the high-affinity (calcium-dependent) interaction of the HC and LC of FVa. We propose that the introduced substitutions disrupt the calcium-binding site in FV, thereby yielding a FV molecule that rapidly loses activity following thrombin-catalyzed activation most likely via dissociation of the HC and LC. 相似文献
25.
Mark L Lee WH Spiller OB Proctor D Blackbourn DJ Villoutreix BO Blom AM 《The Journal of biological chemistry》2004,279(43):45093-45101
Kaposi's sarcoma-associated human herpesvirus (KSHV) is thought to cause Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Previously, we reported that the KSHV complement control protein (KCP) encoded within the viral genome is a potent regulator of the complement system; it acts both as a cofactor for factor I and accelerates decay of the C3 convertases (Spiller, O. B., Blackbourn, D. J., Mark, L., Proctor, D. G., and Blom, A. M. (2003) J. Biol. Chem. 278, 9283-9289). KCP is a homologue to human complement regulators, being comprised of four complement control protein (CCP) domains. In this, the first study to identify the functional sites of a viral homologue at the amino acid level, we created a three-dimensional homology-based model followed by site-directed mutagenesis to locate complement regulatory sites. Classical pathway regulation, both through decay acceleration and factor I cleavage of C4b, required a cluster of positively charged amino acids in CCP1 stretching into CCP2 (Arg-20, Arg-33, Arg-35, Lys-64, Lys-65, and Lys-88) as well as positively (Lys-131, Lys-133, and His-135) and negatively (Glu-99, Glu-152, and Asp-155) charged areas at opposing faces of the border region between CCPs 2 and 3. The regulation of the alternative pathway (via factor I-mediated C3b cleavage) was found to both overlap with classical pathway regulatory sites (Lys-64, Lys-65, Lys-88 and Lys-131, Lys-133, His-135) as well as require unique, more C-terminal residues in CCPs 3 and 4 (His-158, His-171, and His-213) and CCP 4 (Phe-195, Phe-207, and Leu-209). We show here that KCP has evolved to maintain the spatial structure of its functional sites, especially the positively charged patches, compared with host complement regulators. 相似文献
26.
We developed and evaluated simple sequence repeat (SSR) markers derived from expressed sequence tags (ESTs) of Liriodendron tulipifera. Characteristics of 15 EST‐SSR loci were investigated using 33 L. tulipifera individuals. The number of alleles per locus ranged from two to five. The expected and observed heterozygosities ranged from 0.216 to 0.751 and from 0.182 to 0.97, respectively. These loci were further tested for their cross‐species transferability to Liriodendron Chinense. Because of their high level of polymorphism and transferability, our 15 single‐locus EST‐SSR markers will be valuable tools for research on mating system, population genetics and systemic evolution of Liriodendron. 相似文献
27.
28.
CINO PERTOLDI STUART F. BARKER AKSEL BO MADSEN HANNE JØRGENSEN ETTORE RANDI JOAQUÍN MUÑOZ HANS J. BAAGOE VOLKER LOESCHCKE 《Biological journal of the Linnean Society. Linnean Society of London》2008,93(3):457-464
A spatio-temporal study of genetic variation in the Danish pine marten ( Martes martes ) populations from the Jutland peninsula and from the island of Sealand was performed using 11 microsatellite markers. Samples obtained from 1892 to 2003 were subdivided into historical (prior to 1970) and recent (from 1970) groups. As compared with the historical samples, there was a significant loss of genetic variation in the recent Jutland population, but not in Sealand. Effective population sizes were estimated using Bayesian-based software (TMVP). Historical effective population sizes were 5897 (90% highest probability density, HPD, limits: 1502–6849) in Jutland and 1300 (90% HPD limits: 224–5929) in Sealand, whereas recent effective population sizes were 14.7 (90% HPD limits: 10.9–23.5) in Jutland and 802 (90% HPD limits: 51.8–5510) in Sealand. Significant genetic differentiation ( F ST ) was found between the two historical samples, between the two recent samples, and between the historical and the recent sample in Jutland; whereas the F ST value between the historical and the recent sample in Sealand was not significant. The significant genetic differentiation between the historical and the recent samples indicates changes in the genetic compositions over time, and the higher F ST values between the two recent samples, as compared with the two historical samples, indicates that the populations in Sealand and Jutland have drifted apart within a short time span. No deviation from Hardy–Weinberg equilibrium was found within populations, indicating no further substructuring. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society , 2008, 93 , 457–464. 相似文献
29.
热激蛋白90在植物发育和疾病抗性中的作用 总被引:3,自引:0,他引:3
相对分子质量90000的热激蛋白(heatshock protein,HSP90)是真核细胞必需的分子伴侣。拟南芥中HSP90有7个成员,其中AtHSP90-1、AtHSP90-2、AtHSP90-3和AtHSP90-4组成细胞质亚族;AtHSP90-5、AtHSP90-6、AtHSP90-7分别位于叶绿体、线粒体和内质网。HSP90分子伴侣复合物在植物发育和对外部刺激应答中非常重要,尤其是在抗性(resistance R)蛋白介导的抵抗病毒侵入的过程中起重要作用。 相似文献
30.
Steen M Tran S Autin L Villoutreix BO Tholander AL Dahlbäck B 《The Journal of biological chemistry》2008,283(30):20805-20812
Activated coagulation factor V functions as a cofactor to factor Xa in the conversion of prothrombin to thrombin. Based on the introduction of extra carbohydrate side chains in recombinant factor V, we recently proposed several regions in factor Va to be important for factor Xa binding. To further define which residues are important for factor Xa binding, we prepared fifteen recombinant factor V variants in which clusters of charged amino acid residues were mutated, mainly to alanines. The factor V variants were expressed in COS-1 cells, and their functional properties evaluated in a prothrombinase-based assay, as well as in a direct binding test. Four of the factor V variants, 501A/510A/511D, 501A/510A/511D/513A, 513A/577A/578A, and 501A/510A/511D/513A/577A/578A exhibited markedly reduced factor Xa-cofactor activity tested in the prothrombinase assay, and reduced binding affinity as judged by the direct binding assay. These factor Va variants were normally cleaved at Arg-506 by activated protein C, and the interaction between the factor Xa-factor Va complex and prothrombin was unaffected by the introduced mutations. Based on the integration of all available data, we propose a key factor Xa binding surface to be centered on Arg-501, Arg-510, Ala-511, Asp-513, Asp-577, and Asp-578 in the factor Va A2 domain. These residues form an elongated charged factor Xa binding cluster on the factor Va surface. 相似文献