全文获取类型
收费全文 | 9394篇 |
免费 | 859篇 |
国内免费 | 1220篇 |
出版年
2024年 | 24篇 |
2023年 | 100篇 |
2022年 | 228篇 |
2021年 | 365篇 |
2020年 | 306篇 |
2019年 | 374篇 |
2018年 | 328篇 |
2017年 | 262篇 |
2016年 | 338篇 |
2015年 | 550篇 |
2014年 | 649篇 |
2013年 | 694篇 |
2012年 | 908篇 |
2011年 | 829篇 |
2010年 | 547篇 |
2009年 | 529篇 |
2008年 | 575篇 |
2007年 | 508篇 |
2006年 | 440篇 |
2005年 | 418篇 |
2004年 | 327篇 |
2003年 | 302篇 |
2002年 | 296篇 |
2001年 | 169篇 |
2000年 | 166篇 |
1999年 | 118篇 |
1998年 | 116篇 |
1997年 | 69篇 |
1996年 | 76篇 |
1995年 | 79篇 |
1994年 | 67篇 |
1993年 | 54篇 |
1992年 | 62篇 |
1991年 | 48篇 |
1990年 | 51篇 |
1989年 | 43篇 |
1988年 | 47篇 |
1987年 | 39篇 |
1986年 | 31篇 |
1985年 | 36篇 |
1984年 | 31篇 |
1983年 | 26篇 |
1982年 | 26篇 |
1981年 | 18篇 |
1980年 | 14篇 |
1979年 | 18篇 |
1977年 | 16篇 |
1974年 | 16篇 |
1972年 | 16篇 |
1971年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
141.
The effects of thyroid hormone and growth hormone on microsomal testosterone 7 alpha-hydroxylase, P-450a, were studied to understand the interaction of these hormone-mediated regulations in rats. In Western blots using anti-P-450a IgG, 1.7-fold higher content of P-450a was observed in livers of female than male adult rats, while no appreciable sex-related difference was detected in prepubertal rats and rats of 24 months of age. Treatment with n-propyl-2-thiouracil or thyroidectomy of male rats increased by 2-fold the hepatic content of P-450a, but neither regimen had a significant effect on the content in female rats. Levels of P-450a in both sexes of thyroidectomized rats were decreased by the supplementation of triiodothyronine (T3, 50 micrograms per kg, i.p. for 7 days) to levels similar to that observed in normal male rats. Hypophysectomy also caused an increase in microsomal P-450a content in male rats. Continuous infusion of human growth hormone, which mimicked the female secretion, further significantly increased the content in hypophysectomized rats to a level similar to that observed in normal female rats. In contrast, hepatic level of P-450a in hypophysectomized male and female rats was reduced by intermittent injection, which mimicked the male secretion. Clear suppression on the level of hepatic P-450a was also observed by the treatment of hypophysectomized rats with 5 or 50 micrograms/kg of T3 and of hGH-infused hypophysectomized rat with 50 micrograms/kg of T3.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
142.
Selective modulation of band 4.1 binding to erythrocyte membranes by protein kinase C 总被引:7,自引:0,他引:7
We have studied the effects of band 4.1 phosphorylation on its association with red cell inside-out vesicles stripped of all peripheral proteins. Band 4.1 bound to these vesicles in a saturable manner, and binding was characterized by a linear Scatchard plot with an apparent Kd of 1-2 x 10(-7) M. Phosphorylation of band 4.1 by purified protein kinase C reduced its ability to bind to membranes, resulting in a reduction in the apparent binding capacity of the membrane by 60-70% but little or no change in the apparent Kd of binding. By contrast, phosphorylation of band 4.1 by cAMP-dependent kinase had no effect on membrane binding. Digestion of the stripped inside-out vesicles with trypsin cleaved 100% of the cytoplasmic domain of band 3 but had little or no effect on glycophorin. Binding of band 4.1 to these digested vesicles was reduced by 70%. Phosphorylation of band 4.1 by protein kinase C had no effect on its binding to the digested vesicles, suggesting that the cytoplasmic domain of band 3 contained the phosphorylation-sensitive binding sites. This was confirmed by direct measurement of band 4.1 binding to the purified cytoplasmic domain of band 3. Phosphorylation of band 4.1 by protein kinase C reduced its binding to the purified 43-kDa domain by as much as 90%, while phosphorylation by cAMP-dependent kinase was without effect. These results show a selective effect of protein kinase C phosphorylation on the binding of band 4.1 to one of its membrane receptors, band 3, and suggest a mechanism whereby one of the key red cell-skeletal membrane associations may be modulated. 相似文献
143.
Identification of a membrane glycoprotein overexpressed in murine lymphoma sublines resistant to cis-diamminedichloroplatinum(II) 总被引:2,自引:0,他引:2
A series of murine thymic lymphoma cell sublines was selected in vitro for resistance to cis-diamminedichloroplatinum(II) (CDDP). The level of CDDP resistance correlated with reduced drug accumulation in these cells. A rabbit antiserum was raised against the plasma membrane of a CDDP-resistant subline and used in Western blot analyses. Increased expression of a surface antigen of approximately 200 kDa was observed and found to correlate with the degree of resistance. Further biochemical and immunological studies demonstrated that this is a plasma membrane glycoprotein. However, it is different from the multidrug resistance-associated P-glycoprotein with a molecular weight of about 170,000. We have called this unique CDDP resistance-associated membrane protein CPR-200. 相似文献
144.
The polyadenylated RNA directing the synthesis of the rat myelin basic proteins is present in both free and membrane-bound forebrain polyribosomes. 总被引:7,自引:2,他引:5
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Free and membrane-bound polyribosomes were isolated from the forebrain of actively myelinating 24-day-old rats. The poly(A)+ RNA (polyadenylated RNA) extracted from both fractions was translated in vitro in reticulocyte lysates [Hall & Lim (1981) Biochem. J. 196. 327-336] in the presence or absence of a heterologous microsomal membrane fraction from dog pancreas. The rat myelin basic proteins synthesized in vitro were isolated by CM-cellulose chromatography and by immunoprecipitation with purified anti-(myelin basic protein) antibody. The large (mol.wt. 18 500) and small (mol.wt. 16 000) myelin basic proteins were translational products of poly(A)+ RNA from both free and membrane-bound polyribosomes. The identity of the myelin basic proteins was verified by analysis of peptides generated by the cathepsin D digestion of the immunoprecipitated proteins synthesized in vitro, in comparison with authentic rat myelin basic proteins. Although several other translational products of membrane-bound polyribosomal poly(A)+ RNA were modified when microsomal membranes were present during translation, molecular weights of the myelin basic proteins themselves were unchanged. The myelin basic proteins synthesized in vitro also did not differ significantly in size from the authentic myelin basic proteins, indicating that these membrane proteins are unlikely to be synthesized as substantially larger precursor molecules. The presence of the specific mRNA species on both free and membrane-bound polyribosomes is compatible with the extrinsic location of the myelin basic proteins on the cytoplasmic surface of the myelin membrane. 相似文献
145.
Genetic instability of R plasmids in relation to the shift of drug resistance patterns in Salmonella johannesburg 总被引:2,自引:0,他引:2
Observation of the resistance of Salmonella johannesburg to the six drugs ampicillin (A), streptomycin (S), tetracycline (T), chloramphenicol (C), kanamycin(K) and sulphadiazine (Su) was made over the 7 years from 1973 to 1979. Strains with ASTCKSu- and ASCKSu- resistance patterns predominated in the years 1973-1975 and 1976-1979, respectively. These resistances were found to be mediated by autotransferring plasmids belonging to the incompatibility group FIme. The ASTCKSu-resistance plasmids were unstable, giving rise to deletion variants at a much higher frequency than ASCKSu-resistance plasmids either of natural origin or derived in vitro from the ASTCKSu-resistance plasmids. Thus, the ASCKSu-resistance plasmid might be a deletion variant of the ASTCKSu-resistance plasmid. This is supported by the extensive similarity of their cleavage patterns produced by specific restriction endonucleases. 相似文献
146.
Genetic specificity of DNA synthesized in the absence of T4 bacteriophage gene 44 protein. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Upon infection of Escherichia coli B with T4 phage with DO amber mutation in gene 44, a minimal amount of phage DNA is synthesized. This progeny DNA is, for the most part, covalently attached to the parental DNA. Analysis of the genetic representation of this DNA was performed by hybridization to cloned genetic segments. It was shown that areas preferentially replicated differ from origins observed in "normal" replication: under normal conditions, there is a strong origin in the genetic area of genes 50-5 and lack of initiation within the group of genes 40-43 and 35-52. In contrast, in the absence of the gene 44 protein, the genetic area of 50-5 is underrepresented, genes 35-36, tRNA, and genes 40-41 are the most prominent among progeny DNA, and the area of gene 39 is least represented. Since the area of gene 35 is known from the genetic data or other to be a high-frequency recombination area, and since the area of gene 39 is known to display a low frequency of recombination, we postulate that the observed uptake of label occurs at the site-specific recombinational intersections. 相似文献
147.
3-O-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-N- (tert-butyloxycarbonyl)-L-serine was synthesized and condensed by the solid-phase procedure to give the sequence Gly-[beta-D-GlcpNAc-(1 leads to 3)-Ser]-Ala-OH and beta-D-GlcpNAc-(1 leads to 3)-Ser-13-somatostatin. The synthetic glycopeptides appeared homogeneous on t.l.c. and l.c. examination and showed the correct amino acid composition and 2-amino-2-deoxy-D-glucose content. The structure of Gly-[beta-D-GlcpNAc-(1 leads to 3)-Ser]-Ala-OH was further confirmed by mass spectrometry of the N-acetyl permethyl derivative, and by n.m.r. spectroscopy. 相似文献
148.
Solid phase synthesis of somatostatin-28 总被引:10,自引:0,他引:10
N Ling F Esch D Davis M Mercado M Regno P Bohlen P Brazeau R Guillemin 《Biochemical and biophysical research communications》1980,95(3):945-951
The synthesis of ovine hypothalamic somatostatin-28 (Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-Arg-Lys-Ala-Gly--OH) has been accomplished by solid phase methodology. The structure of the synthetic material was verified by: (1) direct sequence analysis with a Beckman 89°C sequencer, (2) correlation of the amino acid analyses of the isolated tryptic peptide fragments with their theoretical compositions, and (3) comparison, using high performance liquid chromatography, of the synthetic methionine-sulfoxide and methionine-sulfone modified NH2-terminal peptides (residues 1–11) with the corresponding tryptic fragment from somatostatin-28. 相似文献
149.
S Lavielle N Ling P Brazeau R Benoit T Wasada D Harris R Unger R Guillemin 《Biochemical and biophysical research communications》1979,91(2):614-622
The synthesis by solid-phase methodology of two glycosylated analogs of somatostatin [Glc-Asn5]-SS and [NAcGlc-Asn5]-SS is described. These two analogs have been biologically tested on the secretion of pituitary growth hormone, pancreatic glucagon and insulin. The results show that glycosylation of somatostatin on the Asn5 residue decreases by a hundred fold the inhibition activity on GH release when tested . , since the activity is similar to somatostatin the carbohydrates are probably removed by some enzymatic reaction and thus liberate the full activity of somatostatin. 相似文献
150.
ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα
下载免费PDF全文
![点击此处可从《Cell biochemistry and function》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Chien‐Yao Fu Wei‐Wen Kuo Tsung‐Jung Ho Su‐Ying Wen Ling‐Chun Lin Yan‐Shen Tseng Hui‐Chuan Hung Vijaya Padma Viswanadha Chih‐Yang Huang 《Cell biochemistry and function》2016,34(8):606-612
ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα. 相似文献