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31.
Glucagon desensitization of adenylate cyclase and stimulation of inositol phospholipid metabolism does not involve the inhibitory guanine nucleotide regulatory protein Gi, which is inactivated upon challenge of hepatocytes with glucagon. 总被引:2,自引:1,他引:1 下载免费PDF全文
G J Murphy D J Gawler G Milligan M J Wakelam N J Pyne M D Houslay 《The Biochemical journal》1989,259(1):191-197
Brief exposure of hepatocytes to glucagon, angiotensin or the protein kinase C activator TPA (12-O-tetradecanoylphorbol 13-acetate) caused the inactivation of the inhibitory guanine nucleotide regulatory protein Gi. Glucagon-mediated desensitization of glucagon-stimulated adenylate cyclase activity was seen in hepatocytes from both normal rats and those made diabetic with streptozotocin, where Gi is not functionally expressed. Normal glucagon desensitization was seen in hepatocytes from young animals, 6 weeks of age, which had amounts of Gi in their hepatocyte membranes which were some 45% of that seen in mature animals (3.4 pmol/mg of plasma-membrane protein). Streptozotocin-induced diabetes in young animals abolished the appearance of functional Gi in hepatocyte plasma membranes. Pertussis-toxin treatment of hepatocytes from both normal mature animals and those made diabetic, with streptozotocin, blocked the ability of glucagon or angiotensin or TPA to elicit desensitization of adenylate cyclase. The isolated B (binding)-subunit of pertussis toxin was ineffective in blocking desensitization. Neither induction of diabetes nor treatment of hepatocytes with pertussis toxin inhibited the ability of glucagon and angiotensin to stimulate the production of inositol phosphates in intact hepatocytes. Thus (i) Gi does not appear to play a role in the molecular mechanism of glucagon desensitization in hepatocytes, (ii) the G-protein concerned with receptor-stimulated inositol phospholipid metabolism in hepatocytes appears not to be a substrate for the action of pertussis toxin, (iii) in intact hepatocytes, treatment with glucagon and/or angiotensin can elicit the inactivation of the inhibitory G-protein Gi, and (iv) pertussis toxin blocks desensitization by a process which does not involve Gi. 相似文献
32.
Dissociation of tissue inhibitor of metalloproteinases (TIMP) from enzyme complexes yields fully active inhibitor. 总被引:4,自引:0,他引:4 下载免费PDF全文
Recombinant human tissue inhibitor of metalloproteinases (TIMP) forms complexes with high-Mr active recombinant stromelysin that are stable over long periods under physiological conditions. TIMP-stromelysin complexes could be dissociated in the presence of EDTA at pH 3, releasing free TIMP and destroying stromelysin activity. The dissociated TIMP was apparently unmodified, in contrast with other known protein inhibitors of metalloproteinases and many classes of serine-proteinase inhibitor, which are slowly cleaved. 相似文献
33.
Common mechanisms of promoter recognition by RNA polymerases II and III 总被引:26,自引:0,他引:26
34.
DNA-DNA homology among lactose- and sucrose-fermenting transconjugants from Lactococcus lactis strains exhibiting reduced bacteriophage sensitivity. 总被引:1,自引:1,他引:0 下载免费PDF全文
DNA-DNA homology between a reduced bacteriophage sensitivity (Rbs+) probe and DNA from both Rbs+ and Rbs- Lactococcus lactis strains was examined. Homology was detected between the probe and five plasmids (pCI750, pCC34, pEB56, pNP2, and pJS88) isolated from lactose-positive Rbs+ transconjugants and between the probe and genomic DNA of a sucrose-positive Rbs+ transconjugant. Additionally, hybridizations conducted between the probe and plasmids reported to encode abortive bacteriophage infection indicated homology with pTR2030 but not with pBF61 and pGBK17. The results suggest that a common genetic determinant(s) may be present in a variety of lactococcal plasmids coding for Rbs+. 相似文献
35.
Glutathione- or sulfhydryl-dependent antioxidant factors that act to prevent lipid peroxidation have been reported in both microsomes and cytoplasm from rat liver. The cytoplasmic factor has been identified in several other tissues and species, but the distribution of the microsomal factor has not been reported. Chicken and mouse livers had much lower activities of the glutathione-dependent membrane-associated and cytoplasmic antioxidant factors than rat liver. Peroxidative damage to membranes has been hypothesized as a mechanism of tissue damage in muscular dystrophy. However, neither the chicken, mouse, nor rat had significant activities of the antioxidant factors in muscle. There was also no significant difference between normal and dystrophic chicken livers in the activity of the antioxidant factors associated with the microsomes or the cytoplasm, nor of the liver microsomal factor in normal and dystrophic mice. The results do not support an important role for the antioxidant factors in the pathogenesis of muscular dystrophy, and raise questions as to whether such factors are physiologically important in species other than rat or in tissues other than liver. 相似文献
36.
Cerebrospinal fluid (CSF) production results from active transport of Na+ from blood to CSF, which is followed by H2O and anions. Amiloride reduces Na+ movement in epithelial tissues. To ascertain if amiloride alters transport of Na+ in the choroid plexus, the drug was administered either i.p. to male Sprague-Dawley rats that were bilaterally nephrectomized to determine in vivo effects, or added to artificial CSF to incubate the choroid plexus in vitro. Choroid cell [Na+] was reduced after amiloride treatment both in vivo and in vitro. In addition, the rate of 22Na uptake into the CSF and choroid plexus (CP) was decreased after amiloride. Alterations in choroid cell [Na+] and 22Na penetration into CSF and CP occurred at relatively high doses of drug (1 mumol/ml, in vitro and 100 micrograms/g in vivo), but lower doses were less effective (0.1 mumol/ml in vitro and 10 micrograms/g in vivo). It is concluded that the effects of amiloride on Na+ distribution and transport in the CP are due to inhibition of basolateral Na+-H+ exchange. 相似文献
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40.
Conformations of the central transforming region (Ile 55-Met 67) of the p21 protein and their relationship to activation of the protein 总被引:1,自引:0,他引:1
J M Chen G Lee P W Brandt-Rauf R B Murphy K D Gibson H A Scheraga S Rackovsky M R Pincus 《International journal of peptide and protein research》1990,36(3):247-254
The GTP-binding p21 protein, encoded by the ras-oncogene, becomes transforming if amino acid substitutions are made at critical positions in the polypeptide chain, e.g., at Gly 12, Gly 13, Ala 59, Gln 61 and Glu 63. Most of these substitutions occur in two phosphate-binding loop regions, Tyr 4-Thr 20, herein designated as segment 1, and Ile 55-Met 67, herein designated, as segment 2. These two segments are homologous to two corresponding regions in the two purine nucleotide binding proteins, bacterial elongation factor (EF-tu) (Val 12-Thr 28 corresponds to segment 1; His 78-Ile 92 corresponds to segment 2) and adenylate kinase (ADK) (Lys 9-Cys 25 corresponds to segment 1 and Tyr 95-Arg 107 corresponds to segment 2). We find that the conformations of the segment 1 region in the p21 protein, EF-tu and ADK are similar to one another and that the conformation of the segment 2 region of EF-tu is superimposable on that of segment 2 of ADK. Furthermore, the relative position of the two segments in EF-tu is strikingly similar to that of the two segments in ADK. In the originally proposed X-ray structure for the p21 protein, the conformation of segment 2 in the p21 protein is not similar to that found for the other two proteins, and its disposition relative to segment 1 and the remainder of the protein is also different from that observed for the other two proteins.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献