全文获取类型
收费全文 | 1105篇 |
免费 | 17篇 |
国内免费 | 5篇 |
出版年
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 10篇 |
2019年 | 13篇 |
2018年 | 17篇 |
2017年 | 7篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 46篇 |
2013年 | 87篇 |
2012年 | 32篇 |
2011年 | 46篇 |
2010年 | 35篇 |
2009年 | 44篇 |
2008年 | 52篇 |
2007年 | 50篇 |
2006年 | 36篇 |
2005年 | 45篇 |
2004年 | 29篇 |
2003年 | 35篇 |
2002年 | 24篇 |
2001年 | 12篇 |
2000年 | 24篇 |
1999年 | 18篇 |
1998年 | 23篇 |
1997年 | 21篇 |
1996年 | 10篇 |
1995年 | 15篇 |
1994年 | 19篇 |
1993年 | 16篇 |
1992年 | 13篇 |
1991年 | 15篇 |
1990年 | 18篇 |
1989年 | 19篇 |
1988年 | 17篇 |
1987年 | 13篇 |
1986年 | 18篇 |
1985年 | 35篇 |
1984年 | 31篇 |
1983年 | 24篇 |
1982年 | 28篇 |
1981年 | 16篇 |
1980年 | 16篇 |
1979年 | 11篇 |
1978年 | 9篇 |
1977年 | 10篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 5篇 |
排序方式: 共有1127条查询结果,搜索用时 15 毫秒
1.
S. Usha 《Journal of biomolecular structure & dynamics》2013,31(7):1474-1492
We have analyzed the nonbonded interactions of the structurally similar moieties, adenine and guanine forming complexes with proteins. The results comprise (a) the amino acid–ligand atom preferences, (b) solvent accessibility of ligand atoms before and after complex formation with proteins, and (c) preferred amino acid residue atoms involved in the interactions. We have observed that the amino acid preferences involved in the hydrogen bonding interactions vary for adenine and guanine. The structural variation between the purine atoms is clearly reflected by their burial tendency in the solvent environment. Correlation of the mean amino acid preference values show the variation that exists between adenine and guanine preferences of all the amino acid residues. All our observations provide evidence for the discriminating nature of the proteins in recognizing adenine and guanine. 相似文献
2.
[3H]Dihydroergocryptine ([3H]DHE) was shown to bind to sites in membranes from neuroblastoma X glioma hybrid cells (NG 108-15) that had the characteristics expected of alpha-adrenergic receptors. The binding was saturable with 0.3 pmol [3H]DHE bound per mg of protein and of high affinity, with an apparent dissociation constant (KD) of 1.8 nM. The specificity of the binding site for various ligands was more similar to that of alpha 2 receptors than to that of alpha 1. No specific binding of [3H]WB-4101 was found in the membranes derived from NG 108 cells. This finding also indicated that the [3H]DHE binding site in the cell is the alpha 2 receptor. GTP lowered the affinity of agonists for the [3H]DHE binding site, although the nucleotide hardly affected the affinity of antagonists including [3H]DHE. 相似文献
3.
T. de la Rubia J. Gonzalez-Lopez J. Moreno M. V. Martinez-Toledo A. Ramos-Cormenzana 《Archives of microbiology》1987,147(4):354-357
The effect of a low phosphate concentration on intracellular adenine nucleotide content, oxygen consumption and poly--hydroxybutyrate deposition was investigated with N-free and NH
4
+
batch cultures of Azotobacter vinelandii. When the microorganisms were cultured under low-phosphate concentrations the cells contained much larger amounts of poly--hydroxybutyrate, but displayed lower oxygen consumption activities and energy charge values than did control cells. Also, the ratio ATP to ADP was much higher in control cells and the intracellular levels of ATP were lower in low-phosphate cells. 相似文献
4.
Kenneth A. Marx Ray Kruger Michael J. Clarke 《Molecular and cellular biochemistry》1989,86(2):155-162
The goal of this study is to establish the nature of pentammineruthenium(III) binding to DNA in intact mouse liver nuclei. Also, we wish to determine whether the nucleosomal organization of mouse chromatin has a substantial effect on the relative Ru(III) binding levels of internucleosomal and nucleosomal core DNA. These questions are important because ammineruthenium compounds share chemical and biological properties with the cis-dichlorodiammineplatinum(II) or cisplatin chemotherapeutic agent. Therefore, they represent a potential class of new chemotherapeutic agents. We find that in intact nuclei the predominant DNA binding site for pentammineruthenium(II), followed by air oxidation to pentammineruthenium(III), is N-7 guanine, as is the case with cisplatin. Also, the Ru(III) distribution between internucleosomal and nucleosomal core DNA was found to be nearly identical as probed with three non-specific deoxyribonucleases. 相似文献
5.
Differential Regulation by Calmodulin of Basal, GTP-, and Dopamine-Stimulated Adenylate Cyclase Activities in Bovine Striatum 总被引:3,自引:1,他引:2
Jeffrey K. Harrison Cynthia K. Mickevicius Margaret E. Gnegy 《Journal of neurochemistry》1988,51(2):345-352
The concentration requirements of calmodulin in altering basal, GTP-, and dopamine-stimulated adenylate cyclase activities in an EGTA-washed particulate fraction from bovine striatum were examined. In the bovine striatal particulate fraction, calmodulin activated basal adenylate cyclase activity 3.5-fold, with an EC50 of 110 nM. Calmodulin also potentiated the activation of adenylate cyclase by GTP by decreasing the EC50 for GTP from 303 +/- 56 nM to 60 +/- 10 nM. Calmodulin did not alter the maximal response to GTP. The EC50 for calmodulin in potentiating the GTP response was only 11 nM as compared to 110 nM for activation of basal activity. Similarly, calmodulin increased the maximal stimulation of adenylate cyclase by dopamine by 50-60%. The EC50 for calmodulin in eliciting this response was 35 nM. These data demonstrate that calmodulin can both activate basal adenylate cyclase and potentiate adenylate cyclase activities that involve the activating GTP-binding protein, Ns. Mechanisms that involve potentiation of Ns-mediated effects are much more sensitive to calmodulin than is the activation of basal adenylate cyclase activity. Potentiation of GTP-stimulated adenylate cyclase activity by calmodulin was apparent at 3 and 5 mM MgCl2, but not at 1 or 10 mM MgCl2. These data further support a role for calmodulin in hormonal signalling and suggest that calmodulin can regulate cyclic AMP formation by more than one mechanism. 相似文献
6.
Lalit K. Srivastava Samina B. Bajwa Rodney L. Johnson Ram K. Mishra 《Journal of neurochemistry》1988,50(3):960-968
The role of the hypothalamic tripeptide L-prolyl-L-leucyl-glycinamide (PLG) in modulating the agonist binding to bovine striatal dopamine D2 receptor was investigated using a selective high-affinity agonist, n-propylnorapomorphine (NPA). PLG caused an enhancement in [3H]NPA binding in striatal membranes in a dose-dependent manner, the maximum effect being observed at 10(-7)-10(-6) M concentration of the tripeptide. The Scatchard analysis of [3H]NPA binding to membranes preincubated with 10(-6) M PLG revealed a significant increase in the affinity of the agonist binding sites. In contrast, there was no effect of PLG on the binding pattern of the antagonist [3H]spiroperidol. The antagonist versus agonist competition curves analyzed for agonist high- and low-affinity states of the receptor displayed an increase in the population and affinity of the high-affinity form of the receptor with PLG treatment. The low-affinity sites concomitantly decreased with relatively small change in the affinity for the agonists. Almost similar results were obtained when either NPA or apomorphine was used in the competition experiments. A partial antagonistic effect of PLG on 5'-guanylylimidodiphosphate [Gpp(NH)p]-induced inhibition of high-affinity agonist binding was also observed, as the ratio of high- to low-affinity forms of the receptor was significantly higher in the PLG-treated membranes compared to the controls. Direct [3H]NPA binding experiments demonstrated that PLG attenuated the Gpp(NH)p-induced inhibition of agonist binding by increasing the EC50 of the nucleotide (concentration that inhibits 50% of the specific binding). No effect of PLG on high-affinity [3H]NPA binding, however, could be observed when the striatal membranes were preincubated with Gpp(NH)p.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
7.
Characterization of Neurotensin Binding Sites in Intact and Solubilized Bovine Brain Membranes 总被引:1,自引:0,他引:1
Analysis of the equilibrium binding of [3H]-neurotensin(1-13) at 25 degrees C to its receptor sites in bovine cortex membranes indicated a single population of sites with an apparent equilibrium dissociation constant (KD) of 3.3 nM and a density (Bmax) of 350 fmol/mg protein (Hill coefficient nH = 0.97). Kinetic dissociation studies revealed the presence of a second class of sites comprising less than 10% of the total. KD values of 0.3 and 2.0 nM were obtained for the higher and lower affinity classes of sites, respectively, from association-dissociation kinetic studies. The binding of [3H]neurotensin was decreased by cations (monovalent and divalent) and by a nonhydrolysable guanine nucleotide analogue. Competition studies gave a potency ranking of [Gln4]neurotensin greater than neurotensin(8-13) greater than neurotensin(1-13). Smaller neurotensin analogues and neurotensin-like peptides were unable to compete with [3H]neurotensin. Stable binding activity for [3H]neurotensin in detergent solution (Kd = 5.5 nM, Bmax = 250 fmol/mg protein, nH = 1.0) was obtained in 2% digitonin/1 mM Mg2+ extracts of membranes which had been preincubated (25 degrees C, 1 h) with 1 mM Mg2+ prior to solubilization. Association-dissociation kinetic studies then revealed the presence of two classes of sites (KD1 = 0.5 nM, KD2 = 3.6 nM) in a similar proportion to that found in the membranes. The solubilized [3H]-neurotensin activity retained its sensitivity to cations and guanine nucleotide. 相似文献
8.
Glutathione reductase fromSaccharomyces cerevisiae undergoes redox interconversionin situ andin vivo
José Peinado Javier Florindo J. López-Barea 《Molecular and cellular biochemistry》1992,110(2):135-143
Redox interconversion of glutathione reductase was studiedin situ withS. cerevisiae. The enzyme was more sensitive to redox inactivation in 24 hour-starved cells than in freshly-grown ones. While 5 μM NADPH
or 100 μM NADH caused 50% inactivation in normal cells in 30 min, 0.75 μM NADPH or 50 μM NADH promoted a similar effect in
starved cells. GSSG reactivated the enzyme previously inactivated by NADPH, ascertaining that the enzyme was subjected to
redox interconversion. Low EDTA concentrations fully protected the enzyme from NADPH inactivation, thus confirming the participation
of metals in such a process. Extensive inactivation was obtained in permeabilized cells incubated with glucose-6-phosphate
or 6-phosphogluconate, in agreement with the very high specific activities of the corresponding dehydrogenases. Some inactivation
was also observed with malate, L-lactate, gluconate or isocitrate in the presence of low NADP+ concentrations.
The inactivation of yeast glutathione reductase has also been studiedin vivo. The activity decreased to 75% after 2 hours of growth with glucono-δ-lactone as carbon source, while NADPH rose to 144%
and NADP+ fell to 86% of their initial values. Greater changes were observed in the presence of 1.5 μM rotenone: enzymatic activity
descended to 23% of the control value, while the NADH/NAD+ and NADPH/NADP+ ratios rose to 171% and 262% of their initial values, respectively. Such results indicate that the lowered redox potential
of the pyridine nucleotide pool existing when glucono-δ-lactone is oxidized promotesin vivo inactivation of glutathione reductase. 相似文献
9.
Ramon Latorre Juan Bacigalupo Ricardo Delgado Pedro Labarca 《Journal of bioenergetics and biomembranes》1991,23(4):577-597
Four different nucleotide-gated ion channels are discussed in terms of their biophysical properties and their importance in cell physiology. Channels activated directly by cGMP are present in vertebrate and invertebrate photoreceptors. In both cases cGMP increases the fraction of time the channel remains in the open state. At least three cGMP molecules are involved in channel opening in vertebrate photoreceptors and the concentration of the cyclic nucleotide to obtain the half maximal effect is about 15 µM. The light-dependent channel of both vertebrates and invertebrates is poorly cation selective. The vertebrate channel allows divalent cations to pass through 10–15-fold more easily than monovalent ions. In agreement with their preference for divalent cations, this channel is blocked byl-cis Dialtazem, a molecule that blocks certain types of calcium channels. In olfactory neurons a channel activated by both cAMP and cGMP is found and, as in the light-dependent channel, several molecules of the nucleotide are needed to open the channel with a half maximal effect obtained in the range of 1–40 µM. The channel is poorly cationic selective. A K+ channel directly and specifically activated by cAMP is found inDrosophila larval muscle. At least three cAMP molecules are involved in the opening reaction. Half-maximal effect is obtained at about 50 µM. This channel is blocked by micromolar amount of tetraethylammonium applied internally. Interestingly, this channel has a probability of opening 10–20-fold larger in the mutantdunce, a mutant that possesses abnormally elevated intracellular cAMP level, than in the wild type. 相似文献
10.
The energy status of mammalian cells is a finely regulated phenomenon. This is especially true in cardiac muscle cells in which energy requirements are high and the system must provide rapid turnover of the adenine nucleotides and instant response to changes in energetic demands. We have examined the acute response of the rat myocardium to ventricular pacing up to 2.5 times the resting heart rate. The purpose of this study was to determine at what level of pacing the normal energy status could be maintained and at what point it was compromised. Myocardial energy charge (EC = (ATP + 0.5 ADP)/(ATP + ADP + AMP)) was maintained at 1, 1.5 and 2 times the resting heart rate but declined significantly at 2.5 times. In contrast, phosphorylation potential (PP = ATP/ADP1 × Pi) was drastically altered in hearts paced at 1.5, 2 and 2.5 times the resting rate. Tissue lactate increased and glycogen decreased in a linear fashion as pacing rate increased, indicating that the metabolic challenge was proportional to the pacing rate. EC seems to reflect the overall status of the cell and its ability to maintain a dynamic equilibrium. PP may reflect the immediate and necessary driving force for mitochondrial respiration in times of increased demand. These data suggest that the myocardium may meet the increased energy demands of acute ventricular pacing by shifting the molar ratio of ATP to ADP times Pi in favour of driving phosphorylation. 相似文献