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521.
The in vitro interaction between the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and cytoskeletal elements is well documented. To verify this association within cells, the intracellular distribution of GAPDH under various metabolic conditions has been investigated in immunostained cells or cells expressing GAPDH as a GFP fusion protein. GAPDH was homogeneously distributed in the cytoplasm and no interaction of GAPDH with cytoskeletal elements, neither with microfilaments nor microtubules or intermediate filaments, was detectable. In living cells expressing GFP-GAPDH, stress fibres were excluded from the fluorescence. In contrast to proliferating cells, the cytoplasmic GAPDH of serum-depleted cells was not homogeneously distributed, but colocalised with stress fibres. The mechanism for stimulating this actin-binding affinity was independent of the NO-signalling pathway. The results support the idea of a specialised function for the interaction of GAPDH and cytoskeletal elements, rather than a general function, as e.g. microcompartmentalization of glycolytic enzymes. 相似文献
522.
The GapC products of Streptococcus agalactiae, Streptococcus dysgalactiae, and Streptococcus uberis share considerable homology at the DNA and amino acid levels. The high similarity at the protein level suggests that one GapC protein might be used as a single antigen to protect dairy cows against infections with the contagious S. agalactiae and the environmental S. dysgalactiae and S. uberis strains. Despite their similarities, immunization with the S. dysgalactiae GapC did not protect dairy cows from a challenge with S. uberis, suggesting the presence of regions in GapC that are involved in species-specific protection. To produce a single antigen that can be used to protect against all streptococcal mastitis infections, we constructed a GapC chimeric protein using the S. uberis GapC product as the backbone followed by non-conserved peptide regions from the S. agalactiae and S. dysgalactiae GapC proteins. We report that the chimeric GapC protein retains the enzymatic activity of the S. uberis GapC protein. In addition, we fused the chimera to the OmpF and LipoF transport sequences of Escherichia coli and the GapC chimeras were present in membrane fractions of E. coli. These extracts could be the basis of an antigen preparation for use in mastitis vaccines. 相似文献
523.
The inhibition of glycolysis by 2,3-dinitrilo-1,4-dithia-9,10-antraquinone (DDA) in Ehrlich ascites carcinoma (EAC) cells as well as in the investigated respiratory and fermentative strains of yeasts was found to be the result of inactivation of thiol enzymes of this pathway. Increasing concentration of DDA caused, in EAC cells, marked inhibition of hexokinase (HK), phosphofructokinase (PFK) and practically total inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). These three enzymes, as well as alcohol dehydrogenase (ADH) were also inactivated by DDA in yeasts. DDA inhibited the biosynthetic processes as measured by following the rate of [14C]adenine and [14C)]valine incorporation into TCA-precipitable fractions proportionally to the degree of glucose consumption by EAC or the yeast cells. 相似文献
524.
A chicken glyceraldehyde 3-phosphate dehydrogenase (GAPDH) processed pseudogene was identified by inverse PCR using oligonucleotide
primers specific for the 5′ region of the GAPDH mRNA. Molecular cloning and sequence analysis of this genomic sequence shows
that the processed pseudogene is incomplete and arranged in a permuted tail-to-head order. We propose that the tail-to-head
organization is the result of circularization and breakage of a GAPDH retrogene prior to chromosomal integration. PCR analysis
of DNAs from quail, pheasant, and various jungle fowl, shows that the processed pseudogene was formed after the three genera
diverged but prior to Gallus speciation. This is the first report of a chicken GAPDH processed pseudogene sequence. This is also the first published report
of a processed pseudogene with a tail-to-head organization.
Received: 15 November 1996 / Accepted: 1 April 1997 相似文献
525.
Robert T. Mallet Young-Hee Kang Naoki Mukohara Rolf Bünger 《生物化学与生物物理学报:疾病的分子基础》1992,1139(3):239-247
Cytosolic free magnesium (Mgf) is considered relatively constant. To test this concept, Mgf was estimated during hyperkalemic ventricular akinesis, normal and maximum adrenergic stimulation, and sulfate loading of the normoxic perfused guinea-pig heart. The Mgf estimates utilized a new sliding scale derived from the Mg2+-dependence of glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase (GAPDH/PGK). The pseudo constant KGAPDH′·KPGK′ was measured as ([creatine phosphate][3-phosphoglycerate][lactate]KLDH/([creatine][Pi[glyceraldehyde 3-phosphate][pyruvate]KCK), which varied with magnesium due to KCK (CK, LDH = creatine kinase, lactate dehydrogenase). However, the correct magnesium dependencies of the true constants KGAPDH·KPGK and KCK were taken from the literature. The [Mg2+] at which pseudo KGAPDH′·KPGK′ equalled true KGAPDH·KPGK was the best estimate of Mgf. Mgf fell to ≈0.13 mM in hyperkalemic arrest from a control of ≈0.6 mM, rising to ≈0.85 mM only during maximum adrenergic stress. Mgf increased further to ≈1.3 mM during sulfate loading which induced ATP catabolism. Mgf and ATP were reciprocally related. Thus; (1) myocardial free [Mg2+] judged from GAPDH/PGK mass-action relations changed appreciably only under extreme physiological states; (2) ATP was a major chelator of Mg2+ in perfused myocardium, i.e., acute ATP pool size reduction may be associated with increments in Mgf. 相似文献
526.
Wang YT Chuang JY Shen MR Yang WB Chang WC Hung JJ 《Journal of molecular biology》2008,380(5):869-885
Although specificity protein 1 (Sp1) accumulation has been found in various tumor strains, its mechanism is still not very clear. Herein, we found that modification of Sp1 by SUMO-1 facilitates Sp1 degradation. Our findings revealed that, although the amounts of Sp1 and Sp1 mutant (K16R) [Sp1(K16R)] mRNA in cells were equal, the protein level of Sp1(K16R) was higher than that of wild-type Sp1. We also proved that this sumoylation site was not the residue at which ubiquitination occurred. Invitro and in vivo pull-down assays revealed that more sumoylated Sp1 was localized in the cytoplasm, and the interaction between SUMO-1-Sp1 and the proteasome subunit rpt6 in HeLa cells was enhanced. In addition, although Sp1 accumulated in the tumorous cervical tissue, it was not prone to sumoylation. Finally, by overexpression of HA (hemagglutinin)-SUMO-1-Sp1-myc, HA-Sp1-myc, and HA-Sp1(K16R), we found that modification of Sp1 by SUMO-1 was important for Sp1 proteolysis. In conclusion, modification of Sp1 by SUMO-1 altered its localization and then increased its interaction with rpt6. This interaction increased the efficiency of Sp1 proteolytic processing and ubiquitination and then resulted in Sp1 degradation. Therefore, sumoylation of Sp1 is attenuated during tumorigenesis in order to increase Sp1 stability. 相似文献
527.
528.
Selenium stimulates pancreatic beta-cell gene expression and enhances islet function 总被引:1,自引:0,他引:1
Campbell SC Aldibbiat A Marriott CE Landy C Ali T Ferris WF Butler CS Shaw JA Macfarlane WM 《FEBS letters》2008,582(15):2333-2337
The present study investigated the role of selenium in the regulation of pancreatic beta-cell function. Utilising the mouse beta-cell line Min6, we have shown that selenium specifically upregulates Ipf1 (insulin promoter factor 1) gene expression, activating the -2715 to -1960 section of the Ipf1 gene promoter. Selenium increased both Ipf1 and insulin mRNA levels in Min6 cells and stimulated increases in insulin content and insulin secretion in isolated primary rat islets of Langerhans. These data are the first to implicate selenium in the regulation of specific beta-cell target genes and suggest that selenium potentially promotes an overall improvement in islet function. 相似文献
529.
Varga A Szabó J Flachner B Roy B Konarev P Svergun D Závodszky P Périgaud C Barman T Lionne C Vas M 《Biochemical and biophysical research communications》2008,366(4):994-1000
l-Nucleoside-analogues, mirror images of the natural d-nucleosides, are a new class of antiviral and anticancer agents. In the cell they have to be phosphorylated to pharmacologically active triphosphate forms, the last step seems to involve human 3-phosphoglycerate kinase (hPGK). Here we present a steady state kinetic and biophysical study of the interaction of the model compound l-MgADP with hPGK. l-MgADP is a good substrate with kcat and Km values of 685 s−1 and 0.27 mM, respectively. Double inhibition studies suggest that l-MgADP binds to the specific adenosine-binding site and protects the conformation of hPGK molecule against heat denaturation, as detected by microcalorimetry. Structural details of the interaction in the enzyme active site are different for the d- and l-enantiomers (e.g. the effect of Mg2+), but these differences do not prevent the occurrence of the catalytic cycle, which is accompanied by the hinge-bending domain closure, as indicated by SAXS measurements. 相似文献
530.