全文获取类型
收费全文 | 16033篇 |
免费 | 593篇 |
国内免费 | 409篇 |
出版年
2023年 | 118篇 |
2022年 | 216篇 |
2021年 | 273篇 |
2020年 | 283篇 |
2019年 | 483篇 |
2018年 | 523篇 |
2017年 | 225篇 |
2016年 | 316篇 |
2015年 | 449篇 |
2014年 | 906篇 |
2013年 | 1068篇 |
2012年 | 567篇 |
2011年 | 1018篇 |
2010年 | 728篇 |
2009年 | 826篇 |
2008年 | 867篇 |
2007年 | 939篇 |
2006年 | 854篇 |
2005年 | 780篇 |
2004年 | 639篇 |
2003年 | 598篇 |
2002年 | 507篇 |
2001年 | 370篇 |
2000年 | 322篇 |
1999年 | 343篇 |
1998年 | 375篇 |
1997年 | 282篇 |
1996年 | 254篇 |
1995年 | 257篇 |
1994年 | 219篇 |
1993年 | 175篇 |
1992年 | 153篇 |
1991年 | 126篇 |
1990年 | 109篇 |
1989年 | 96篇 |
1988年 | 85篇 |
1987年 | 78篇 |
1986年 | 44篇 |
1985年 | 84篇 |
1984年 | 125篇 |
1983年 | 84篇 |
1982年 | 73篇 |
1981年 | 46篇 |
1980年 | 39篇 |
1979年 | 29篇 |
1978年 | 15篇 |
1977年 | 14篇 |
1976年 | 10篇 |
1975年 | 10篇 |
1974年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
51.
Danielle L. Laval-Martin Isabelle A. Carr Saverio J. Barbera Leland N. Edmunds 《Chronobiology international》1990,7(2):99-105
-We have previously shown that NAD kinase and NADP phosphatase activities display circadian rhythms, in the soluble (SN) and membrane-bound (P) fractions of crude extracts of the achlorophyllous ZC mutant of the phytoflagellate Euglena gracilis (which displays circadian rhythmicity of cell division). We determined if changes in the affinity of NADP phosphatase and NAD kinase for their substrates, NADP+ and NAD+, were occurring by calculating the ratios 100(velocity found in Km conditions/velocity found in saturating conditions). The rationale was that if the affinity remained unchanged according to circadian time (CI), these values should always equal 50, independently of any changes in enzyme quantity; values greater than 50 should indicate increases in enzyme affinity, and values less than 50 decreases in affinity. Our results indicated that these values calculated for NADP phosphatase exhibited a complex pattern of rhythmicity, while those for NAD kinase displayed circadian variations strongly correlated with the rhythms in enzyme activity. The curves showed troughs at CT 00-04 both in dividing and nondividing cells and peaks at CT 18-20 or at CT 08-14 in cells sampled, respectively, from a dividing or a stationary culture. Such variations are indicative of changes in the kinetic properties of the enzyme, which may reflect modifications in its affinity either for effectors (such as Ca2+-calmodulin) or for its substrate, NAD+. This may be due to (i) the expression of different isoenzymes at different CTs; (ii) different posttranslational modifications of the enzyme; or (iii) concentrations of effectors varying in a circadian manner. 相似文献
52.
Kunio Yonemasu Takako Sasaki Yoshiko Dohi Charles M. Lapière Betty Nusgens 《生物化学与生物物理学报:疾病的分子基础》1990,1096(1):47-51
C1q, a collagen-like complement protein, was purified from the serum of a ddermatosparactic calf which lacks procollagen N-terminal proteinase (pN-proteinase). The specific hemolytic activity of the serum Clq from the dermatosparactic animal was identical to that of C1q from a normal calf. Gel-filtration of serum from dermatosparactic calf, on Sepharose 6B, showed the presence of C1q-antigenic material at only one position which was identical to the elution position of normal bovine C1q. No differdence, under dissociating conditions, could be seen in the size of the chains of C1q in specific immunoprecipitates isolated from the sera of dermatosparactic and normal animals, as judged by polyacrylamidegel electrophoresis (PAGE) in the presence of sodium dodecyl sulfate (SDS). The C1q from the dermatosparactic animal showed the same N-terminal amino acid and typtic-digest peptide pattern on HPLC as C1q from the normal calf. These results strongly suggest that pN-proteinase is not involved in the extracellular processing of C1q. 相似文献
53.
Summary Arginine kinase (AK) is present throughout the life cycle of Drosophila melanogaster, but there is a sharp, transient peak of AK activity during the prepupal period and a second period of elevated activity at the time of eclosion of the adult. Imaginal discs show the greatest increase in AK activity at the prepupal stage of those tissues assayed. The prepupal peak is not seen when the temperature-sensitive ecdysoneless mutant ecd-1 is shifted to 29° C at mid-third instar larval stage. The peak in activity reappears when ecd-1 is either shifted back to 20° C after 60 h at 29° C or is fed 20-hydroxyecdysone. At the restrictive temperature, imaginal discs from ecd-1 larvae progressively lose AK activity, whereas discs from 20-hydroxyecdysone-fed larvae have a marked increase in AK activity at stage P3 of the prepupal period. These data suggest that the prepupal peak is regulated by the hormone 20-hydroxyecdysone. 相似文献
54.
Evangelia G. Kranias Ramesh C. Gupta Gyorgyi Jakab Hae Won Kim Nancy A. E. Steenaart Stephen T. Rapundalo 《Molecular and cellular biochemistry》1988,82(1-2):37-44
Summary Canine cardiac sarcoplasmic reticulum is phosphorylated by adenosine 3,5-monophosphate (cAMP)-dependent and by calcium · calmodulin-dependent protein kinases on a 27 000 proteolipid, called phospholamban. Both types of phosphorylation are associated with an increase in the initial rates of Ca2+ transport by SR vesicles which reflects an increased turnover of elementary steps of the calcium ATPase reaction sequence. The stimulatory effects of the protein kinases on the calcium pump may be reversed by an endogenous protein phosphatase, which can dephosphorylate both the CAMP-dependent and the calcium · calmodulin-dependent sites on phospholamban. Thus, the calcium pump in cardiac sarcoplasmic reticulum appears to be under reversible regulation mediated by protein kinases and protein phosphatases. 相似文献
55.
Summary The actions of cyclic AMP are subject to several levels of post-receptor modulation in cardiac tissue. Isoproterenol and prostaglandin E1 both stimulate cAMP accumulation, but only isoproterenol causes activation of particulate cAMP-dependent protein kinase, leading to activation of phosphorylase kinase and glycogen phosphorylase, and inhibition of glycogen synthase. Through the use of isolated, adult ventricular myocytes, we have determined that the hormone-specific activation of glycogen phosphorylase is due to subcellular compartmentation of cAMP. There is some evidence that cyclic nucleotide phosphodiesterases, whose activity is stimulated by alpha1-adrenergic agonists in isolated myocytes, may have a role in compartmentation. Phosphoinositide hydrolysis is stimulated by alpha, and muscarinic agonists, presumably leading to activation of protein kinase C, which in turn has multiple effects on hormone-sensitive adenylate cyclase.Abbreviations cAMP
Adenosine-3,5-Cyclic Monophosphate
- cGMP
Guanosine-3,5-Cyclic Monophosphate
- Gi, GS
Guanine nucleotide-binding proteins linked to inhibition and stimulation, respectively, of adenylate cyclase
- GTP
Guanosine-5-triphosphate
- PDE
Cyclic Nucleotide Phosphodiesterase
- PGE1
Prostaglandin E1 相似文献
56.
The N-terminal -amino groups of 1-bungarotoxin (1-Bgt) fromBungarus multicinctus venom were modified with trinitrobenzene sulfonic acid and the modified derivative was separated by high performance liquid chromatography. The trinitrophenylated (TNP) derivative contained two TNP groups at the -amino groups of A chain and B chain and showed a marked decrease in enzymatic activity. Methionine residues at positions 6 and 8 of the A chain were oxidized with chloramine T or cleaved with cyanogen bromide to remove the N-terminal octapeptide. Oxidation of methionine residues and removal of the N-terminal octapeptide caused a precipitous decrease in enzymatic activity, whereas antigenicity remained unchanged. The presence of dihexanoyllecithin influenced the interaction between 1-Bgt and 8-antilinonaphthalene sulfonate (ANS) and revealed that 1-Bgt consists of two types of ANS-binding sites, one at the substrate binding site of the A chain and the other might be at the B chain. The modified derivatives still retained their affinity for Ca2+ and ANS, indicating that the N-terminal region is not involved in Ca2+ and substrate binding. A fluorescence study revealed that the -amino group of the A chain was in the vicinity of substrate binding site and that the TNP -amino groups were in proximity to Trp-19 of the A chain. In addition, the study showed that the N-terminal region is important for stabilizing the architectural environment of Trp-19. The results, together with the proposal that Trp-19 of the A chain is involved in substrate binding, suggest that the N-terminal region of the A chain plays a crucial role in maintaining a functional active site for 1-Bgt. 相似文献
57.
Alberto Alcázar Elena Martin Juan López-Fando Dr. Matilde Salinas 《Neurochemical research》1988,13(9):829-836
A simple and short purification procedure applicable to casein kinase II has been developed, for fully characterizing the enzyme from calf cerebral cortex cytosol. The procedure consists of four chromatographic steps: DEAE-cellulose, phosphocellulose, phosvitin-Sepharose and ATP-agarose which yields 87% pure casein kinase II. The purified enzyme shows three major bands with apparent molecular masses of 42, 38, and 27 kDa by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and is self-autophosphorylated on its 27 kDa polypeptide. The enzyme shows all the characteristics described for casein kinase II from other sources: it is independent of cyclic nucleotides, calcium/phospholipids, and double-stranded poly(I).poly(C); it can utilize both ATP and GTP as phosphoryl donors and can phosphorylate both casein and phosvitin but not histone. The kinetic studies establish that theK
m for ATP is 12.5 M and 25.1 M when using phosvitin and casein respectively as phosphoryl acceptors. TheK
m for phosvitin is 0.91 mg/ml and for casein 1.43 mg/ml, while theV
max is 315 nmol/min/per mg protein and 479 nmol/min/per mg protein for phosvitin and casein respectively. The activity of the kinase is highly stimulated by KCl or NaCl, and almost completely inhibited by heparin concentrations of 1 g/ml (92%). This inhibition is reduced to only 33% in the presence of optimal KCl concentrations (150 mM). Spermine stimulates enzyme activity, whilst hemin produces a slight inhibition. 相似文献
58.
Akhlaq A. Farooqui Tahira Farooqui Allan J. Yates Lloyd A. Horrocks 《Neurochemical research》1988,13(6):499-511
Protein kinase C has recently attracted considerable attention because of its importance in the control of cell division, cell differentiation, and signal transduction across the cell membrane. The activity of this enzyme is altered by several lipids such as diacylglycerol, free fatty acids, lipoxins, gangliosides, and sulfatides. These lipids may interact with protein kinase C either directly or through calcium ions and produce their regulatory effect (activation or inhibition) on the activities of the enzymes phosphorylated by this kinase. These processes widen our perspective of the regulation of intercellular and intracelluular communication.Abbreviations used (PK-C)
Protein kinase C
- (cAMP-PK)
cAMP dependent protein kinase
- (DAG)
diacylglycerol
- (PtdSer)
phosphatidylserine
- (InsP
3)
inositol 1,4,5-trisphosphate
- (PtdIns 4,5-P2)
inositol 4,5 bisphosphate
- (FFA)
free fatty acid
- (MBP)
myelin basic protein
- (ATP)
adenosine triphosphate
- (GTP)
guanine triphosphate
- (TPA)
12-tetradecanoylphorbol-13-acetate
- (EGF)
epidermal growth factor
- (PDGF)
platelet derived growth factor
- (NeuNAc)
and N-acetylneuraminic acid 相似文献
59.
Scott T. Sayers Hock C. Yeoh Jerry A. McLane Irene R. Held 《Neurochemical research》1988,13(12):1125-1131
The acetylcholine receptor (AChR) content and the autorphosphorylation of the regulatory subunit of cyclic AMP-dependent protein kinase type II (R-II) were evaluated in rat soleus muscles at 24, 30 and 66 hr after surgical denervation by cutting the nerve at a short distance (short-nerve-stump) and at a long distance (long-nerve-stump) from the muscle. AChR content was based on the specific binding of [125I]alpha-bungarotoxin (BUTX); changes in the autophosphorylation of R-II were based upon the predominant in vitro32P-phosphorylation of a 56-Kd soluble protein in cytosolic fractions of solei. The AChR content and the32P-autophosphorylation of R-II were increased in samples from short-nerve-stump solei, but not from long-nerve-stump solei, after a denervation-time of 30 hr. This nerve-stump-length dependency indicates that the two denervation effects are not related to the immediate halt of impulse-evoked muscle contractility. Furthermore, the results show that alterations in the32P-autophosphorylation of R-II occurred before, as well as whenever, increases in the AChR content were found. Speculatively, this temporal relationship may be significant with respect to the potential role of R-II in gene expression.Abbreviations ACh
acetylcholine
- AChR
acetylcholine receptor(s)
- BUTX
alpha-bungarotoxin
- Kd
kilodalton
- PAGE
polyacrylamide gel electrophoresis
- R-II
regulatory subunit of cyclic AMP-dependent protein kinase type II
- SDS
sodium dodecyl sulfate 相似文献
60.
S.M. Teresa Hernndez-Sotomayor Marina Macías-Silva Magdalena PlebanÜski J. Adolfo García-Sinz 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1988,972(3)
In hepatocytes obtained from hypothyroid rats, phorbol myristate acetate (PMA) and vasopressin diminished the accumulation of cyclic AMP and the stimulation of ureagenesis induced by isoprenaline or glucagon without altering significantly the accumulation of cyclic AMP induced by forskolin. Pretreatment with PMA markedly reduced the stimulation of ureagenesis and the accumulation of cyclic AMP induced by isoprenaline or glucagon. In membranes from cells pretreated with PMA, the stimulation of adenylate cyclase induced by isoprenaline + GTP, glucagon + GTP or by Gpp[NH]p were clearly diminished as compared to the control, whereas forskolin-stimulated activity was not affected. The data indicate heterologous desensitization of adenylate cyclase. It was also observed that the homologous (García-Sáinz J.A. and Michel, B. (1987) Biochem. J. 246, 331–336) and this heterologous β-adrenergic desensitizations were additive. Pertussis toxin treatment markedly reduced the heterologous desensitization of adenylate cyclase but not the homologous β-adrenergic desensitization. It is concluded that the homologous and heterologous desensitizations involve different mechanisms. The homologous desensitization seems to occur at the receptor level, whereas the heterologous probably involves the guanine nucleotide-binding regulatory protein, Ns. 相似文献