全文获取类型
收费全文 | 181326篇 |
免费 | 11257篇 |
国内免费 | 92篇 |
出版年
2021年 | 1721篇 |
2020年 | 1030篇 |
2019年 | 1300篇 |
2018年 | 2465篇 |
2017年 | 2484篇 |
2016年 | 4979篇 |
2015年 | 9791篇 |
2014年 | 9975篇 |
2013年 | 10573篇 |
2012年 | 11701篇 |
2011年 | 8880篇 |
2010年 | 6407篇 |
2009年 | 6151篇 |
2008年 | 6499篇 |
2007年 | 6486篇 |
2006年 | 6141篇 |
2005年 | 11777篇 |
2004年 | 10372篇 |
2003年 | 8456篇 |
2002年 | 5825篇 |
2001年 | 2233篇 |
2000年 | 1237篇 |
1999年 | 2640篇 |
1998年 | 1686篇 |
1997年 | 1130篇 |
1995年 | 995篇 |
1992年 | 2742篇 |
1991年 | 2731篇 |
1990年 | 2784篇 |
1989年 | 2688篇 |
1988年 | 2611篇 |
1987年 | 2413篇 |
1986年 | 2172篇 |
1985年 | 2414篇 |
1984年 | 1879篇 |
1983年 | 1558篇 |
1982年 | 1281篇 |
1981年 | 1161篇 |
1980年 | 1114篇 |
1979年 | 1588篇 |
1978年 | 1312篇 |
1977年 | 1090篇 |
1976年 | 1114篇 |
1975年 | 1255篇 |
1974年 | 1449篇 |
1973年 | 1440篇 |
1972年 | 1246篇 |
1971年 | 1188篇 |
1970年 | 1046篇 |
1969年 | 1068篇 |
排序方式: 共有10000条查询结果,搜索用时 156 毫秒
991.
Chromosomal DNAs of 26 different strains representing Saccharomyces species were analyzed by pulsed-field gel electrophoresis and subsequent hybridization to Y' telomere DNA. Hybridization to Y' was found exclusively in Saccharomyces cerevisiae strains, and among these strains, Y' sequences were found to be lacking in small, middle-sized, and large chromosomes. 相似文献
992.
cDNA structures and regulation of two interferon-induced human Mx proteins. 总被引:33,自引:2,他引:31 下载免费PDF全文
M Aebi J F?h N Hurt C E Samuel D Thomis L Bazzigher J Pavlovic O Haller P Staeheli 《Molecular and cellular biology》1989,9(11):5062-5072
Human cells treated with interferon synthesize two proteins that exhibit high homology to murine Mx1 protein, which has previously been identified as the mediator of interferon-induced cellular resistance of mouse cells against influenza viruses. Using murine Mx1 cDNA as a hybridization probe, we have isolated cDNA clones originating from two distinct human Mx genes, designated MxA and MxB. In human fibroblasts, expression of MxA and MxB is strongly induced by alpha interferon (IFN-alpha), IFN-beta, Newcastle disease virus, and, to a much lesser extent, IFN-gamma, MxA and MxB proteins have molecular masses of 76 and 73 kilodaltons, respectively, and their sequences are 63% identical. A comparison of human and mouse Mx proteins revealed that human MxA and mouse Mx2 are the most closely related proteins, showing 77% sequence identity. Near their amino termini, human and mouse Mx proteins contain a block of 53 identical amino acids and additional regions of very high sequence similarity. These conserved sequences are also present in a double-stranded RNA-inducible fish gene, which suggests that they may constitute a functionally important domain of Mx proteins. In contrast to mouse Mx1 protein, which accumulates in the nuclei of IFN-treated mouse cells, the two human Mx proteins both accumulate in the cytoplasm of IFN-treated cells. 相似文献
993.
David T. Osuga Milton S. Feather Mena J. Shah Robert E. Feeney 《Journal of Protein Chemistry》1989,8(4):519-528
Amino acids and peptides have been attached to the C-6 hydroxyls of the galactose and the N-acetylgalactosamine by first oxidizing the C-6 hydroxyls to the aldehydes by galactose oxidase in the presence of small amounts of catalase, followed by reductive amination (-amino group) in the presence of cyanoborohydride. The activity of oxidized antifreeze glycoprotein was >70% of the original, and considerable activity has been retained with some substitutions on reductive amination using cyanoborohydride. The following were some activities retained (as compared with the oxidized antifreeze glycoprotein): Gly, 64; (Gly)2, 88; (Gly)3, 82; (Gly)4, 70; Gly-Gly-NH2, 44, Gly-Glu, 13; Gly-Leu, 40; Gly-Tyr, 57; Gly-Gly-Leu, 50; Gly-Gly-Phe, 30; and Gly-Gly-Val, 35. On amino acid analysis of acid hydrolysates, some release of the amino acid attached by amination occurred; e.g., Gly-Tyr gave 0.26 Gly and 0.49 Tyr per disaccharide. 相似文献
994.
Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins. 总被引:8,自引:2,他引:6 下载免费PDF全文
Cathepsin S was detected in bovine kidney, spleen, lymph nodes and lung by immunochemical methods. The immunostaining of cathepsin S in kidney was concentrated to the cells of the proximal tubule, where the enzyme was present in cytoplasmic granules. The purification method for cathepsin S from bovine spleen involved (NH4)2SO4 fractionation, chromatography on CM-Sephadex C-50, gel filtration on Sephacryl S-200 and chromatofocusing (pH 8.0-6.0). The enzyme was partially destroyed by autolysis of the homogenate at pH 4.2. The isoelectric point of cathepsin S was 7.0. Cathepsin S was found to hydrolyse proteins at a similar rate to cathepsin L below pH 7.0. At pH values of 7.0-7.5 cathepsin S retained most of its activity, whereas cathepsin L was completely inactive. 相似文献
995.
Lipid metabolism during the initiation of lactation in the rat. The effects of starvation and tumour growth. 下载免费PDF全文
1. The effects of starvation post partum (24 h) and tumour growth pre partum on the initiation of lactation in the rat were studied. 2. Tumour growth decreased food intake at 24 h, but not at 2 days post partum. 3. Pup growth rate increased with hyperphagia; starvation and tumour burden decreased pup growth, and starvation decreased maternal body weight. 4. Starvation decreased gastrointestinal-tract mass; tumour growth decreased gastrointestinal-tract and mammary-gland mass. 5. Mammary-gland DNA-synthesis rate was high immediately post partum, but decreased by day 3 of lactation; starvation and tumour burden decreased this rate, and also decreased gastrointestinal-tract DNA-synthesis rate. 6. Arteriovenous differences for glucose and lactate across the mammary gland did not change with time, nor were they affected by the tumour. Starvation decreased arterial glucose and lactate, and the gland extracted less glucose but produced lactate. 7. Mammary-gland lipogenesis was sensitive to starvation and to tumour growth. 8. In contrast with the gradual development of mammary-gland lipogenic enzyme activities, lipoprotein lipase activity was high in the gland by 2 days post partum; starvation or tumour burden decreased the activity. 9. The mammary gland is sensitive post partum to decreased food intake, and to tumour presence. The effects of the latter are apparently independent of hypophagia. 相似文献
996.
Reversible thermal inactivation of the quinoprotein glucose dehydrogenase from Acinetobacter calcoaceticus. Ca2+ ions are necessary for re-activation. 下载免费PDF全文
The soluble form of the homogeneous quinoprotein glucose dehydrogenase from Acinetobacter calcoaceticus is reversibly inactivated at temperatures above 35 degrees C. An equilibrium is established between active and denatured enzyme, this depending on the protein concentration and the inactivation temperature used. Upon thermal inactivation the enzyme dissociates into the prosthetic group pyrroloquinoline quinone and the apo form of glucose dehydrogenase. After inactivation at 50 degrees C active enzyme is re-formed again at 25 degrees C. Ca2+ ions are necessary for the re-activation process. The velocity of re-activation depends on the protein concentration, the concentration of the prosthetic group pyrroloquinoline quinone and the Ca2+ concentration. The apo form of glucose dehydrogenase can be isolated, and in the presence of pyrroloquinoline quinone and Ca2+ active holoenzyme is formed. Even though native glucose dehydrogenase is not inactivated in the presence of EDTA or trans-1,2-diaminocyclohexane-NNN'NH-tetra-acetic acid, Ca2+ stabilizes the enzyme against thermal inactivation. Two Ca2+ ions are found per subunit of glucose dehydrogenase. The data suggest that pyrroloquinoline quinone is bound at the active site via a Ca2+ bridge. Mn2+ and Cd2+ can replace Ca2+ in the re-activation mixture. 相似文献
997.
Posttranslational regulation of keratins: degradation of mouse and human keratins 18 and 8. 总被引:34,自引:4,他引:30 下载免费PDF全文
D A Kulesh G Cece?a Y M Darmon M Vasseur R G Oshima 《Molecular and cellular biology》1989,9(4):1553-1565
Human keratin 18 (K18) and keratin 8 (K8) and their mouse homologs, Endo B and Endo A, respectively, are expressed in adult mice primarily in a variety of simple epithelial cell types in which they are normally found in equal amounts within the intermediate filament cytoskeleton. Expression of K18 alone in mouse L cells or NIH 3T3 fibroblasts from either the gene or a cDNA expression vector results in K18 protein which is degraded relatively rapidly without the formation of filaments. A K8 cDNA containing all coding sequences was isolated and expressed in mouse fibroblasts either singly or in combination with K18. Immunoprecipitation of stably transfected L cells revealed that when K8 was expressed alone, it was degraded in a fashion similar to that seen previously for K18. However, expression of K8 in fibroblasts that also expressed K18 resulted in stabilization of both K18 and K8. Immunofluorescent staining revealed typical keratin filament organization in such cells. Thus, expression of a type I and a type II keratin was found to be both necessary and sufficient for formation of keratin filaments within fibroblasts. To determine whether a similar proteolytic system responsible for the degradation of K18 in fibroblasts also exists in simple epithelial cells which normally express a type I and a type II keratin, a mutant, truncated K18 protein missing the carboxy-terminal tail domain and a conserved region of the central, alpha-helical rod domain was expressed in mouse parietal endodermal cells. This resulted in destabilization of endogenous Endo A and Endo B and inhibition of the formation of typical keratin filament structures. Therefore, cells that normally express keratins contain a proteolytic system similar to that found in experimentally manipulated fibroblasts which degrades keratin proteins not found in their normal polymerized state. 相似文献
998.
Protein synthesis, myosin ATPase activity and myofibrillar protein composition in hearts from tumour-bearing rats and mice. 下载免费PDF全文
Growing rats and adult weight-stable mice bearing a transplantable methylcholanthrene-induced sarcoma were compared with animals with various states of malnutrition. Heart protein synthesis was measured in vivo. Myocardial RNA, myofibrillar protein composition and the Ca2+-activated ATPase activity in heavy chains of native myosin were measured. 'Fingerprints' were made from myosin by trypsin treatment to evaluate possible structural changes in the protein. Cardiac protein-synthesis rate was decreased by 20% in growing tumour-bearing rats, by 35% in protein-malnourished (rats) and by 47% in starved rats, compared with freely fed controls (P less than 0.05). Adult tumour-bearing mice showed no significant decrease in myocardial protein synthesis. Pair-weighed control mice had significantly depressed heart protein synthesis. Protein translational efficiency was maintained in both tumour-bearing rats and mice, but was decreased in several groups of malnourished control animals. The Ca2+-activated myosin ATPase activity was decreased in all groups of malnourished animals, including tumour-bearing mice and rats, without any evidence of a change in cardiac isomyosin composition. We conclude that loss of cardiac muscle mass in tumour disease is communicated by both depressed synthesis and increased degradation largely owing to anorexia and host malnutrition. Increased adrenergic sensitivity in hearts from tumour-bearing and malnourished animals is not communicated by increased Ca2+-activated ATPase activity. This may be down-regulated in all groups with malnutrition, without any observable alterations in the isomyosin profile. 相似文献
999.
Enhanced Co2+ activation and inhibitor binding of carboxypeptidase M at low pH. Similarity to carboxypeptidase H (enkephalin convertase). 总被引:2,自引:0,他引:2 下载免费PDF全文
Carboxypeptidases H and M differ in their distribution and other properties, but both are activated by Co2+ and inhibited by guanidinoethylmercaptosuccinic acid. The higher degree of activation or inhibition of carboxypeptidase H by these agents at acid pH has been employed to identify this enzyme in tissues. We found that the activation or inhibition of both purified and plasma-membrane-bound human carboxy-peptidase M depends on the pH of the medium. CoCl2 activated over 6-fold at pH 5.5, but less than 2-fold at pH 7.5. Guanidinoethylmercaptosuccinic acid inhibited the membrane-bound carboxypeptidase M more effectively than the purified enzyme, and the IC50 was about 25-30 times lower at pH 5.5. As purified human plasma carboxypeptidase N and pancreatic carboxypeptidase B were also activated more at pH 5.5, we conclude that the increased activation by CoCl2 is due to the enhanced dissociation of Zn2+ below the pKa of the ligands that co-ordinate the cofactor in the protein. Thus increased activation or inhibition at acid pH would not differentiate basic carboxypeptidases. 相似文献
1000.
Polarity as a criterion in protein design 总被引:6,自引:0,他引:6
Hypothetical proteins can be tested computationally by determining whether or not the designed sequence-structure pair has the characteristics of a typical globular protein. We have developed such a test by deriving quantities with approximately constant value for all globular proteins, based on empirical analysis of the exposed and buried surfaces of 128 structurally known proteins. The characteristic quantities that best appear to segregate badly designed or deliberately misfolded proteins from their properly folded natural relatives are the polar fraction of side chains on the protein surface and, independently, in the protein interior. Three of the seven hypothetical structures tested here can be rejected as having too many polar side-chain groups in the interior or too few on the protein surface. In addition, a recently designed nutritional protein is identified as being very much unlike globular proteins. These database-derived characteristic quantities are useful in screening designed proteins prior to experiment and may be useful in screening experimentally determined (X-ray, NMR) protein structures for possible errors. 相似文献