全文获取类型
收费全文 | 1543篇 |
免费 | 175篇 |
出版年
2022年 | 20篇 |
2021年 | 35篇 |
2020年 | 20篇 |
2019年 | 24篇 |
2018年 | 37篇 |
2017年 | 26篇 |
2016年 | 53篇 |
2015年 | 68篇 |
2014年 | 61篇 |
2013年 | 84篇 |
2012年 | 118篇 |
2011年 | 122篇 |
2010年 | 77篇 |
2009年 | 48篇 |
2008年 | 79篇 |
2007年 | 72篇 |
2006年 | 75篇 |
2005年 | 52篇 |
2004年 | 50篇 |
2003年 | 67篇 |
2002年 | 53篇 |
2001年 | 34篇 |
2000年 | 20篇 |
1999年 | 25篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 11篇 |
1993年 | 10篇 |
1992年 | 20篇 |
1991年 | 22篇 |
1990年 | 17篇 |
1989年 | 20篇 |
1988年 | 17篇 |
1987年 | 17篇 |
1986年 | 13篇 |
1985年 | 18篇 |
1983年 | 10篇 |
1982年 | 10篇 |
1980年 | 8篇 |
1979年 | 13篇 |
1978年 | 10篇 |
1977年 | 8篇 |
1976年 | 15篇 |
1975年 | 9篇 |
1974年 | 16篇 |
1973年 | 9篇 |
1972年 | 8篇 |
1971年 | 9篇 |
1970年 | 11篇 |
1965年 | 8篇 |
排序方式: 共有1718条查询结果,搜索用时 46 毫秒
41.
39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. 总被引:41,自引:0,他引:41
J Herz J L Goldstein D K Strickland Y K Ho M S Brown 《The Journal of biological chemistry》1991,266(31):21232-21238
A 39-kDa protein of unknown function has previously been reported to copurify with the low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor. In this study we demonstrate that a recombinant 39-kDa fusion protein can reversibly bind to the 515-kDa subunit of the LRP/alpha 2-macroglobulin receptor. This interaction inhibits the binding and uptake of the receptor's two known ligands: 1) beta-migrating very low density lipoproteins activated by enrichment with apoprotein E and 2) alpha 2-macroglobulin activated by incubation with plasma proteases or methylamine. A potential in vivo role of the 39-kDa protein is to modulate the uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in hepatic and extrahepatic tissues. 相似文献
42.
Nancy L. Figler Dudley K. Strickland Margaretta Allietta Steven L. Gonias 《Journal of structural biology》1991,106(3)
α2-Macroglobulin (α2M) is a plasma proteinase inhibitor that binds up to 2 mole of proteinase per mole of inhibitor. Proteinase binding or reaction with small primary amines causes a major conformational change in α2M. As a result of this conformational change, a new epitope recognized by monoclonal antibody 7H11D6 is exposed. The association of α2M-proteinase or α2M-methylamine with α2M cellular receptors is prevented by 7H11D6. In this investigation, the binding of 7H11D6 to α2M was studied by electron microscopy. 7H11D6 bound to α2M-methylamine and α2M-trypsin but not to native α2M. The structure of α2M after conformational change resembled the letter “H.” 7H11D6 epitopes were identified near the apices of the four arms in the α2M “H” structure. 7H11D6 that was adducted to colloidal gold (7HAu) retained the specificity of the free antibody (binding to α2M-trypsin but not to native α2M). α2M conformational change intermediates prepared by sequential reaction with a protein crosslinker and trypsin also bound 7HAu. These results suggest that a complete α2M conformational change is not necessary for 7H11D6 epitope exposure and may not be required for receptor recognition. 7HAu was used to isolate a preparation consisting primarily of binary α2M-trypsin (1 mole trypsin per mole α2M instead of 2). Structures resembling the letter “H” were most common; however, each field showed some atypical molecules with arms that were compacted instead of thin and elongated. These incompletely transformed structures were similar to the α2M conformational intermediates described previously (S. L. Gonias and N. L. Figler (1989) J. Biol. Chem. 264, 9565–9570). We propose that lateral arm extension is a critical step in α2M conformational change. Failure of lateral arm extension is probably a common property of different α2M conformational intermediates. 相似文献
43.
Transient translational silencing by reversible mRNA deadenylation. 总被引:26,自引:0,他引:26
J Huarte A Stutz M L O'Connell P Gubler D Belin A L Darrow S Strickland J D Vassalli 《Cell》1992,69(6):1021-1030
44.
Single-strand-specific nucleases are a diverse and important group of enzymes that are able to cleave a variety of DNA structures present in duplex molecules. Nuclease SP, an enzyme from spinach, has been purified to apparent homogeneity, allowing for the unambiguous characterization of a number of its physical properties as well as its DNA strand cleavage specificities. The effects of ionic strength, pH, divalent metal cations, and temperature on nuclease SP activity have been examined in detail. Nuclease SP was found to be quite thermostable and could be stimulated by Co2+. In addition, the cleavage of UV-damaged and undamaged supercoiled plasmid substrates under a variety of conditions suggests that at least two types of structures are recognized and processed by nuclease SP: UV photoproduct-induced distortions and unwound "nuclease hypersensitive sites". These studies indicate that nuclease SP is functionally related to other single-strand-specific nucleases and is a potential enzymatic tool for probing and manipulating various types of DNA structures. 相似文献
45.
D K Strickland J D Ashcom S Williams W H Burgess M Migliorini W S Argraves 《The Journal of biological chemistry》1990,265(29):17401-17404
Ten peptides, derived from human alpha 2-macroglobulin (alpha 2M) receptor by chemical or proteolytic digestion, were sequenced. Comparative analysis revealed that all of the resulting sequences were present within the cDNA-deduced structure of low density lipoprotein receptor-related protein (LRP) (Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H., and Stanley, K. K. (1988) EMBO J. 7, 4119-4127). The findings provide evidence that the alpha 2M receptor and LRP are the same molecule. Further evidence comes from immunoprecipitation experiments using a monoclonal antibody specific for the alpha 2M receptor that show this molecule, like LRP, to contain two polypeptides of approximately 420 and 85 kDa that are noncovalently associated. An additional component of this receptor system is a 39-kDa polypeptide that co-purifies with the alpha 2M receptor during affinity chromatography. Solid phase binding studies reveal that the 39-kDa polypeptide binds with high affinity (Kd = 18 nM) to the 420-kDa component of the alpha 2M receptor. The apparent identity of LRP and the alpha 2M receptor suggests that this molecule is a multifunctional receptor with the capacity to bind diverse biological ligands and highlights a possible relationship between two previously unrelated biological processes, lipid metabolism and proteinase regulation. 相似文献
46.
The induction of antigenic changes in a teratocarcinoma stem cell line (F9) by retinoic acid 总被引:6,自引:0,他引:6
Davor Solter Lynne Shevinsky Barbara B. Knowles Sidney Strickland 《Developmental biology》1979,70(2):515-521
Treatment of embryonal carcinoma cells F9 with retinoic acid results in the appearance of epithelioid cells resembling endoderm which synthesize basement membrane protein and plasminogen activator. Concomitant with the appearance of these properties of differentiated cells, the epithelial cells cease to express SSEA-1, an antigenic determinant characteristic of teratocarcinoma stem cells and early mouse embryos. Our evidence indicates that the phenotypic changes that accompany retinoic acid treatment of embryonal carcinoma cells are irreversible and a consequence of the differentiation of the cells into endoderm. 相似文献
47.
P Van Helden W N Strickland W F Brandt C Von Holt 《Biochimica et biophysica acta》1978,533(1):278-281
Histones H2B have been isolated from the terminally differentiated diploid erythrocytes of three different classes, amphibia (Xenopus laevis), reptilia (Crocodilus niloticus) and aves (Gallus domesticus). Partial amino acid sequences revealed three regions of sequence variation, each variant involving a single amino acid substitution. 相似文献
48.
Active transport of inorganic phosphate into whole cells of a strain (AB3311) derived from K12 was found to be partially resistant to 50 μM carbonyl cyanide -chlorophenyl hydrazone (CCCP), a powerful uncoupler of oxidative phosphorylation. The presence of 10 mM dithiothreitol (DTT) before the addition of CCCP completely prevented the inhibition of phosphate uptake caused by the uncoupler. The addition of DTT to the CCCP-inhibited system restored phosphate uptake to the control rate even when added 5 min after the phosphate transport assay was started. This uncoupler resistant transport is insensitive to anaerobiosis, or the addition of 10 mM KCN which reduces oxygen consumption to less than 1% that of aerobic controls. Additional studies of transport in a mutant (CBT302) deficient in membranebound Ca2+-, Mg2+-ATPase activity also demonstrated the retention of appreciable inorganic phosphate uptake under anaerobic conditions. 相似文献
49.
Adenyl cyclase and cyclic nucleotide phosphodiesterase activities were assayed in homogenates of hind leg skeletal muscle from dystrophic and normal mice. Adenyl cyclase activity was stimulated 2.5 times by epinephrine and 6 times by fluoride over the basal activity in both dystrophic and normal mice. The activity of adenyl cyclase from dystrophic muscle of mice was significantly higher than that of normal mice under all the conditions tested (i.e. basal, epinephrine and fluoride). Cyclic nucleotide phosphodiesterase from skeletal muscle of mice has two Km's (2.1 and 11 mumol/l) which suggests the existence of either two forms of enzyme or a single enzyme with negative cooperativity. The activity of this enzyme was significantly elevated in the skeletal muscle of dystrophic mice compared to the normal controls. The available evidence suggests that the same cyclic nucleotide phosphodiesterase is responsible for the hydrolysis of both cyclic AMP and cyclic GMP. 相似文献
50.
Three pelagic marine phytoplankters, Coccolithus huxleyi, Skeletonema costatum, and Thalassiosira rotula, and a facultative heterotroph, Cyclotella cryptica, have been exposed to three organic substrates, viz, glucose, acetate, and glutamate, at low concentrations (organic carbon 0.25 mg/liter). Experiments were performed in the dark and light and the net assimilation of substrate was measured by using radiocarbon. The dark uptake of carbon dioxide was also determined, together with photosynthesis at near optimum light intensity. The expected heterotrophy was detected with Cyclotella cryptica. Thalassiosira rotula was found to assimilate glutamate at an appreciable rate. In all cases, however, the short-term uptake of carbon dioxide in the dark was the greatest assimilation rate measured. Values are discussed in relation to their ecological significance and it is concluded that heterotrophic survival of these and probably most other algae in the open ocean would be impossible unless they were in contact with a high concentration of substrate in the form of particulate matter. 相似文献