全文获取类型
收费全文 | 539篇 |
免费 | 40篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 10篇 |
2015年 | 18篇 |
2014年 | 26篇 |
2013年 | 25篇 |
2012年 | 41篇 |
2011年 | 37篇 |
2010年 | 22篇 |
2009年 | 25篇 |
2008年 | 47篇 |
2007年 | 44篇 |
2006年 | 40篇 |
2005年 | 31篇 |
2004年 | 30篇 |
2003年 | 40篇 |
2002年 | 29篇 |
2001年 | 8篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 5篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1972年 | 1篇 |
1967年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有579条查询结果,搜索用时 62 毫秒
1.
Strategies for signal amplification in nucleic acid detection 总被引:3,自引:0,他引:3
S. Calin Andras J. Brian Power Edward C. Cocking Michael R. Davey 《Molecular biotechnology》2001,19(1):29-44
Many aspects of molecular genetics necessitate the detection of nucleic acid sequences. Current approaches involving target
amplification (in situ PCR, Primed in situ Labeling, Self-Sustained Sequence Replication, Strand Displacement Amplification), probe amplification (Ligase Chain Reaction,
Padlock Probes, Rolling Circle Amplification) and signal amplification (Tyramide Signal Amplification, Branched DNA Amplification)
are summarized in the present review, together with their advantages and limitations. 相似文献
2.
Manfred Keller Andras Seregi Georg Hertting Rolf Jackisch 《Neurochemistry international》1987,10(4):433-443
Prostaglandin (PG) and thromboxane B2 (TXB2) biosynthesis was studied in cultured astrocytes from neonatal rat brain hemispheres. After two weeks of cultivation, prostanoids were formed with the spectrum: PGD2 > TXB2 > PGF2 > PGE2, as measured by specific radioimmunoassays. Under basal conditions PGD2 biosynthesis (9.55 ng/mg protein/15 min) was in the same order of magnitude as the sum of the other prostanoids. The formation of prostanoids was stimulated in a concentration dependent manner (up to 6–10 fold) by the calcium ionophore A 23187 (0.01–10 μM) as well as by melittin (0.01–5 μg/ml), phospholipase A2 (10–40 U/ml) and phospholipase C (0.01–1 U/ml). Basal and evoked PG and TXB2 biosynthesis depended on the availability of Ca2+, as demonstrated in Ca2+ free incubation medium containing Na2EDTA (1 μM), or with verapamil (100 μM) and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)-octylester-HCl (TMB-8, 1–100 μM). Indomethacin (10 μM), mepacrine (100 μM) and p-bromophenacylbromide (50 μ M) inhibited basal and evoked PG formation. Thin-layer chromatography (TLC) detection after incubation of the cells with [3H]arachidonic acid (1 μCi/ml, for 60 min) confirmed the results obtained by radioimmunoassay. Incubation of [3H]arachidonic acid labelled cells with inonophore or phospholipases, followed by lipid extraction and TLC, showed that A 23187 liberated [3H]arachidonic acid predominantly from phosphatidylethanolamine, whereas phospholipase A2 and C reduced mainly the labelling of the phosphatidyl-inositol/-choline fraction. Potassium depolarization of the cells did not enhance prostanoid formation. Similarly, drugs with affinity to - or β-adrenoceptors, or to dopamine-, 5-hydroxytryptamine-, muscarine-, histamine-, glutamate-, aspartate-, GABA, adenosine- and opioid-receptors failed to stimulate prostanoid biosynthesis. Also compounds like angiotensin, bradykinin and thrombin were ineffective in this respect.
In conclusion, our results confirm that cultured astrocytes possess the complete pattern of enzymes necessary for prostanoid formation and hence might play a crucial role in brain prostanoid biosynthesis. Stimulation of prostanoid biosynthesis involves Ca2+-dependent activation of phospholipase A2, cyclooxygenase reaction and further PG metabolism. However, the endogenous stimulus for enhanced prostanoid synthesis in the brain still has to be established. 相似文献
3.
A preparation method has been described to obtain a relatively pure and functionally intact fragmented sarcoplasmic reticulum (SR) vesicles fraction from normal and atrophied muscles. Purified SR preparations from rabbit gastrocnemius muscle atrophied by disuse showed similar protein composition (gel electrophoresis; Laemmli 1970) and similar vanadate induced crystallization (Dux and Martonosi 1983) properties of Ca2+-ATPase as those of control preparations. In the early period of atrophy (1-2 weeks) both the Ca2+-ATPase activity and Ca2+ uptake showed a 2-3-fold increase (from 3.42 +/- 0.24 to 7.34 +/- 0.25 mumol Pi X mg-1 prot X min-1 and from 1.26 +/- 0.10 to 3.36 +/- 0.22 mumol/l Ca2+ X min-1 X mg-1 prot. respectively). 相似文献
4.
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
5.
Transgenic mice carrying the 3-hydroxy-3-methylglutarylCoA reductase (HMG) promoter driving theEscherichia coli -galactosidase (lacZ) gene did not display the expected ubiquitous and constitutive expression inHMG-lacZ transgenic mice. The same promoter is however able to drive ubiquitous expression of the chloramphenicol acetyltransferase (cat) gene. Two lines of doubleHMG-lacZ andHMG-cat transgenic mice were obtained in which the two constructs were integrated at the same genomic sites. These mice expressed both reporter genes, but exclusively in the testes. These results suggest that thelacZ sequence might interfere negatively with the expression of the adjacentHMG-cat transgene. 相似文献
6.
The effect of ethanol on maxi Ca2+-activated K+ channels (BK channels) in GH3 pituitary tumor cells was investigated using single-channel recordings and focusing on intracellular
signal transduction. In outside-out patches, ethanol caused a transient concentration-dependent increase of BK-channel activity.
30 mm (1.4‰) ethanol significantly increased mean channel open time and channel open probability by 26.3 ± 9% and 78.8 ± 10%, respectively;
single-channel current amplitude was not affected by ethanol. The augmenting effect of ethanol was blocked in the presence
of protein kinase C (PKC) inhibitors staurosporine, bisindolylmaleimide, and PKC (19–31) pseudosubstrate inhibitor as well
as by AMP-PNP (5′-adenylylimidodiphosphate), a nonhydrolyzable ATP-analogue, but not by the phospholipase C blocker U-73122.
Phosphatase inhibitors microcystin-LR and okadaic acid promoted the ethanol effect. The blocking effect was released at higher
concentrations of ethanol (100 mm) suggesting a second site of action or a competition between blockers and ethanol. Our results suggest that the effect of
ethanol on BK-channels is mediated by PKC stimulation and phosphorylation of the channels which increases channel activity
and hence may influence action potentials duration and hormone secretion.
Received: 24 July 1996/Revised: 27 December 1996 相似文献
7.
Andras Schaefer Reinhard Zibirre Peter Kabus Jutta Kühne Gebhard Koch 《Bioscience reports》1982,2(8):613-615
After exposure of HeLa cells to poliovirus there is a rapid decline (within minutes) in fluorescence polarization of DPH (1,6-diphenyl-1,3,5-hexatriene). Within one hour after infection the (Na+/K+)ATPase activity of an isolated plasma-membrane-rich fraction is enhanced, the cell volume decreases, and the intracellular concentration of a potent low-molecular-weight inhibitor of host protein synthesis increases. 相似文献
8.
Peter Andras 《PloS one》2012,7(11)
Particle swarm optimization is a popular method for solving difficult optimization problems. There have been attempts to formulate the method in formal probabilistic or stochastic terms (e.g. bare bones particle swarm) with the aim to achieve more generality and explain the practical behavior of the method. Here we present a Bayesian interpretation of the particle swarm optimization. This interpretation provides a formal framework for incorporation of prior knowledge about the problem that is being solved. Furthermore, it also allows to extend the particle optimization method through the use of kernel functions that represent the intermediary transformation of the data into a different space where the optimization problem is expected to be easier to be resolved–such transformation can be seen as a form of prior knowledge about the nature of the optimization problem. We derive from the general Bayesian formulation the commonly used particle swarm methods as particular cases. 相似文献
9.
Authors investigated the in vitro effect of alpha 2-HS-glycoprotein on the lymphoblastic transformation and interleukin-2 production. The observations were made on the peripheral blood lymphocytes of healthy persons, on those of women taking oral contraceptives and on those of patients with systemic lupus erythematosus. The alpha 2-HS-glycoprotein inhibited the mitogen responses both in physiologic and in the halved concentrations. The inhibition of the interleukin-2 production seemed less remarkable. 相似文献
10.
Studies of crayfish chemical ecology have been conducted in both day and night conditions. This variation may hinder the comparison of data among studies, if the responses by crayfish to chemical cues are dependent upon the time at which the cues are encountered. We tested the hypothesis that responses to chemical cues are dependent on observation time using the red swamp crayfish, Procambarus clarkii. Procambarus clarkii is known to exhibit a light-regulated circadian rhythm, with nocturnal activity peaks. Habitat use differed significantly between non-stimulated periods and periods of exposure to a food stimulus, but no effects of photoperiod (normal vs. reversed) or laboratory conditions (dark vs. light) were observed. The results suggest that, all else being equal, (1) studies of crayfish chemical ecology can be successfully conducted in a variety of experimental conditions, and (2) previous studies conducted at various times of the day should have comparable results. 相似文献