全文获取类型
收费全文 | 15396篇 |
免费 | 559篇 |
国内免费 | 384篇 |
出版年
2023年 | 110篇 |
2022年 | 241篇 |
2021年 | 253篇 |
2020年 | 276篇 |
2019年 | 471篇 |
2018年 | 489篇 |
2017年 | 221篇 |
2016年 | 302篇 |
2015年 | 434篇 |
2014年 | 846篇 |
2013年 | 1018篇 |
2012年 | 539篇 |
2011年 | 964篇 |
2010年 | 662篇 |
2009年 | 782篇 |
2008年 | 799篇 |
2007年 | 883篇 |
2006年 | 819篇 |
2005年 | 755篇 |
2004年 | 625篇 |
2003年 | 581篇 |
2002年 | 491篇 |
2001年 | 353篇 |
2000年 | 318篇 |
1999年 | 333篇 |
1998年 | 363篇 |
1997年 | 275篇 |
1996年 | 253篇 |
1995年 | 256篇 |
1994年 | 214篇 |
1993年 | 164篇 |
1992年 | 151篇 |
1991年 | 125篇 |
1990年 | 104篇 |
1989年 | 89篇 |
1988年 | 84篇 |
1987年 | 77篇 |
1986年 | 40篇 |
1985年 | 85篇 |
1984年 | 119篇 |
1983年 | 87篇 |
1982年 | 76篇 |
1981年 | 49篇 |
1980年 | 41篇 |
1979年 | 33篇 |
1978年 | 19篇 |
1977年 | 15篇 |
1976年 | 11篇 |
1975年 | 9篇 |
1974年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 250 毫秒
21.
Influence of Hydrocortisone on Chick Embryo Retina Development 总被引:1,自引:1,他引:0
Renza Vento Giuseppina D'Ancona Michela Giuliano Gennaro Taibi Giovanni Tesoriere 《Journal of neurochemistry》1987,48(6):1693-1698
Treatment of chick embryos in ovo with hydrocortisone-21-phosphate (a single dose of 150 micrograms) caused a marked reduction of retinal thymidine kinase activity 24 h later. The inhibitory effect was highest (65-70%) in 8-10-day-old embryos and declined with age, disappearing after day 15. It was accompanied by a reduction in thickness of the retinal layers. Adrenocorticotropic hormone (ACTH) treatment (10 micrograms daily for 2 days) also produced an age-dependent inhibitory effect on retinal thymidine kinase, whereas treatment with a single dose of 200 micrograms of metopirone, a compound that prevents the 11 beta-hydroxylation of steroid molecules in the adrenal glands, impeded the decrease in thymidine kinase activity that normally occurs in chick embryo retina after day 9 of development. In addition, metopirone prevented the inhibition exerted by ACTH on thymidine kinase activity but had no effect on the action of hydrocortisone. 相似文献
22.
Tyrosine hydroxylase purified from rat pheochromocytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. The extent of activation was correlated with the degree of phosphate incorporated into the enzyme. Comparable stoichiometric ratios (0.6 mol phosphate/mol tyrosine hydroxylase subunit) were obtained at maximal concentrations of either cyclic AMP-dependent or cyclic GMP-dependent protein kinases. The enzymes appeared to mediate the phosphorylation of the same residue based on the observation that incorporation was not increased when both enzymes were present. The major tryptic phosphopeptide obtained from tyrosine hydroxylase phosphorylated by each protein kinase exhibited an identical retention time following HPLC. The purified phosphopeptides also exhibited identical isoelectric points. These data provide support for the notion that the protein kinases are phosphorylating the same residue of tyrosine hydroxylase. 相似文献
23.
24.
Interleukin 2 (IL 2) is a polypeptide growth factor essential for the proliferation and differentiation of T lymphocytes, large granulocytic lymphocytes, and, potentially, cells of the antibody-producing lineage, B lymphocytes. Many of the biological properties of IL 2 may be mimicked or potentiated by a potent class of tumor promoters, phorbol esters. Phorbol esters have recently been shown to associate with and activate a unique phospholipid/Ca2+-dependent phosphotransferase, protein kinase C (PK-C). Utilizing two-dimensional gel electrophoresis, we have compared the IL 2 and diacylglycerol-induced protein phosphorylation patterns of several IL 2-dependent murine cell lines. Both IL 2 and synthetic diacylglycerol, 1-oleyl-2-acetylglycerol (OAG), stimulated phosphorylation of a number of protein substrates in intact cells compared to unstimulated controls. Three groups of substrates were identified; the first showed increased phosphorylation following stimulation with either IL 2 or OAG, while the second and third groups showed increased phosphorylation following stimulation with IL 2 but not OAG, and with OAG but not IL 2, respectively. Here, we characterize the kinetics of phosphorylation of one cellular substrate, p68, which appears to be phosphorylated in response to direct activators of PK-C or lymphoid or myeloid growth factors in their respective lineage cell lines. The observation that IL 2 also stimulates a unique series of phosphoproteins in addition to those induced by direct PK-C activators suggests that IL 2 may initiate additional protein kinase activities, unrelated to PK-C, which may also be critical for the ligand-receptor signal transduction process regulating growth and gene expression. 相似文献
25.
S. L. Macaulay Julie D. Newman J. D. Mc Armstrong J. Bornstein 《Molecular and cellular biochemistry》1987,74(1):95-101
The N-terminal part sequences of pituitary growth hormone, N-acetyl-hGH 7–13 and hGH 6–13, promoted conversion of glycogen synthase b to glycogen synthase a in skeletal muscle and adipose tissue when injected intravenously. The peptides also caused conversion of phosphorylase a to phosphorylase b in liver and adipose tissue, but not in muscle, where the peptides antagonised activation of phosphorylase. Synthase phosphatase activity in muscle and phosphorylase phosphatase activity in liver increased after injection of peptide, with time courses of change similar to those seen for muscle synthase and liver phosphorylase activities. Injection of peptide also decreased both the cyclic AMP dependent and independent synthase kinase activities in muscle. These results show that the insulin-like activities of these peptides on glycogen synthase and phosphorylase involve both increases in protein phosphatase activities and inhibition of protein kinase activities. These results are discussed in relation to the insulin-like activities of growth hormone. 相似文献
26.
During growth on glycerol two marine Desulfovibrio strains that can grow on an unusually broad range of substrates contained high activities of glycerol kinase, NAD(P)-independent glycerol 3-phosphate dehydrogenase and the other enzymes necessary for the conversion of dihydroxyacetone phosphate to pyruvate. Glycerol dehydrogenase and a specific dihydroxyacetone kinase were absent. During growth on dihydroxyacetone, glycerol kinase is involved in the initial conversion of this compound to dihydroxyacetone phosphate which is then further metabolized. Some kinetic properties of the partially purified glycerol kinase were determined. The role of NAD as electron carrier in the energy metabolism during growth of these strains on glycerol and dihydroxyacetone is discussed.Glycerol also supported growth of three out of four classical Desulfovibrio strains tested. D. vulgaris strain Hildenborough grew slowly on glycerol and contained glycerol kinase, glycerol 3-phosphate dehydrogenase and enzymes for the dissimilation of dihydroxyacetone phosphate. In D. gigas which did not grow on glycerol the enzymes glycerol kinase and glycerol 3-phosphate dehydrogenase were absent in lactate-grown cells.Abbreviations DHA
dihydroxyacetone
- DHAP
dihydroxyacetone phosphate
- G3P
glycerol 3-phosphate
- GAP
glyceraldehyde 3-phosphate
- 3-PGA
3-phosphoglycerate
- 2-PGA
2-phosphoglycerate
- 2,3-DPGA
2,3-diphosphoglycerate
- PEP
phosphoenolpyruvate
- DH
dehydrogenase
- GK
glycerol kinase
- DHAK
dihydroxyacetone kinase
- TIM
triosephosphate isomerase
- PGK
3-phosphoglycerate kinase
- PK
pyruvate kinase
- LDH
lactate dehydrogenase
- DTT
dithiotreitol
- HEPES
4-(2-hydroxyethyl)-1-piperazine ethane sulfonic acid
- PIPES
piperazine-1,1-bis(2-ethane sulfonic acid)
- BV2+/BV+
oxidized/reduced benzylviologen
- PMS
phenazine methosulfate
- DCPIP
2,6-dichlorophenolindophenol
- MTT
3-(4,5-dimethylthiazol-2-yl)-2,4-diphenyltetrazolium bromide 相似文献
27.
Expression vectors for cDNA of the κ and λ1 chains of a monoclonal antibody directed against creatine kinase were introduced into murine myeloma cells. κ and γ1 cDNA were either under the control of the SV40 early promoter or of the cognate promoters and enhancers of the light- and heavy-chain genes. Secretion of immuno-reactive κ and γ1 chains into the culture medium was demonstrated with the SV40 promoter as well as with the cognate promoters. Expression of y 1 cDNA with the SV40 early promoter was about twice as high as with the heavy-chain promoter and enhancer. Expression of κ cDNA under the control of the S V40 early promoter was about 17 times higher than with the light-chain promoter and enhancer. These expression levels were compared to those of a genomic immunoglobulin (Ig) κ determinant, including introns. Such an entire κ gene led to expression of the light chain at levels double those with the κ cDNA construction using the SV40 promoter and about 35 times as high when using κ cDNA and the cognate promoter and enhancer. This result might indicate that, besides the cognate promoter and enhancer elements, other intragenic elements are involved in the regulation of Ig expression. However, the SV40 early promoter seems to be able to compensate for the absence of these postulated regulatory elements probably located in the introns. 相似文献
28.
Florence Levy-Favatier Lydie Tichnonicky Jacques Kruh Marc Delpech 《Biochimie》1989,71(11-12):1157-1161
We have previously described in rat liver two protein kinases tightly bound to DNA, one is serine-specific, the other arginine-specific. In this work we show that both enzymes are present in various rat tissues and in liver from various species. Both kinase specific activities are strongly decreased in methyl-DBA-induced hepatomas and in HTC cells but not in regenerating liver after hepatectomy. This decrease is then not related to cell proliferation. 相似文献
29.
Jackie R. Vandenheede Sigrid Staquet Wilfried Merlevede 《Molecular and cellular biochemistry》1989,87(1):31-39
Summary Fractionation of rabbit skeletal muscle cytosol on Aminohexyl-Sepharose has resulted in the identification of a latent ATP, Mg-dependent protein phosphatase whose catalytic subunit is in the active conformation, but is inhibited by the presence of more than one modulator unit. The partially purified enzyme is converted to an inactive, kinase FA-dependent form upon incubation at 30°C unless modulator-specific polyclonal antibodies are added to the preparation. The immunoglobulins also relieve the inhibition which is responsible for the low basal phosphatase activity of the enzyme, and they counteract all of the heat-stable inhibitor activity present in the preparation. Addition of free catalytic subunit abolishes the inhibition of the latent enzyme in a dose-dependent way, but cannot prevent the inactivation process. The inactivated phosphatase and the original latent enzyme exhibit the same apparent M
r in sucrose density-gradient centrifugation (70 000) and in gel filtration (110 000).Abbreviations PMSF
Phenylmethanesulphonyl Fluoride
- TLCK
L-l-chloro-3-(4-tosylamido)-7-amino2-heptanone-hydrochloride
- TPCK
L-l-chloro-3-(4-tosvlamido)-4-phenyl-2-butanone 相似文献
30.
Cholesterylphosphoryldimethylethanolamine is a zwitterionic compound which is a good bilayer stabilizer. As has been found with many other compounds having these properties, cholesterylphosphoryldimethylethanolamine is found to be a potent inhibitor of protein kinase C in both vesicle and micelle assay systems. The kinetics of the inhibition in Triton X-100 micelles was non-competitive with respect to ATP, histone, diolein, phorbol ester and Ca2+. It has a Ki of about 30 m. The inhibition kinetics as a function of phosphatidylserine concentration is more complex but suggestive of competitive inhibition. Cholesterylphosphoryldimethylethanolamine does not prevent the partitioning of protein kinase C into the membrane. This inhibitor lowers the Ca2+-phosphatidylserine-independent phosphorylation of protamine sulfate by protein kinase C and directly affects the catalytic segment of the enzyme generated by tryptic hydrolysis. Thus, this zwitterionic bilayer stabilizing inhibitor of protein kinase C both competes with the binding of phosphatidylserine as well as affects the active site of protein kinase C.Abbreviation CPD
cholesterylphosphoryldimethylethanolamine 相似文献