全文获取类型
收费全文 | 618篇 |
免费 | 48篇 |
出版年
2022年 | 5篇 |
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 11篇 |
2017年 | 15篇 |
2016年 | 20篇 |
2015年 | 17篇 |
2014年 | 28篇 |
2013年 | 39篇 |
2012年 | 81篇 |
2011年 | 92篇 |
2010年 | 46篇 |
2009年 | 26篇 |
2008年 | 20篇 |
2007年 | 23篇 |
2006年 | 20篇 |
2005年 | 18篇 |
2004年 | 14篇 |
2003年 | 22篇 |
2002年 | 11篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 10篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 10篇 |
1985年 | 4篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有666条查询结果,搜索用时 15 毫秒
1.
The systemic injection of kainic acid (KA) has been shown to destroy neurons in the hippocampus and to induce limbic-type seizure activity. However, little is known on the neurochemical events that are associated with this convulsant effect. In the present work we studied the spontaneous and the K+-stimulated release of labeled -aminobutyric acid (GABA), glutamate, serotonin and dopamine, in hippocampal slices of KA-treated rats, at the moment of clinical seizures (2 h) and 72 h later. At the onset of convulsions we found a 40–45% decrease in the K+-stimulated release of GABA. The release of the other neurotransmitters was not significantly affected by KA treatment. After 72 h GABA release was still reduced by 30–40%. It is concluded that the epileptogenic effect of KA in the hippocampus is probably related to a diminished inhibitory GABAergic neurotransmission. 相似文献
2.
Hepatic coma was induced in rats chronically treated with CCl4, by means of a single injection of ammonium acetate. The activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), as well as the synaptosomal uptake and release of [3H]GABA, were measured in the following brain areas of the comatose rats: cortex, striatum, hypothalamus, hippocampus, midbrain and cerebellum. Hepatic coma was associated with a general decrease of GAD activity, whereas GABA-T activity was diminished only in the hypothalamus, striatum and midbrain. During hepatic coma, the K+-stimulated [3H]GABA release was notably diminished in the striatum and cerebellum, whereas a significant increase was observed in the hippocampus. [3H]GABA uptake increased in most regions after CCl4 treatment, independently of the presence of coma. The results indicate that GABAergic transmission seems to be decreased in most cerebral regions during hepatic coma. 相似文献
3.
Summary Twelve cases of lissencephaly are reported. A high resolution chromosome study was performed on each in order to detect small chromosomal anomalies, undetectable with routine techniques. Only one case was shown to have an unbalanced karyotype with a microdeletion of the short arm of chromosome 17(del 17p). This child also had symptoms of the Miller-Dieker syndrome, consisting of lissencephaly, characteristic facies, pre- and post-natal growth retardation and other birth defects. As proposed by Dobyns, it seems justifiable to classify lissencephalies into four different groups, according to other clinical manifestations and results of chromosome studies. 相似文献
4.
We construct a theoretical model of the transition structure for the carboxylation reaction of ribulose-1,5-biphosphate catalyzed by Rubisco. This is a first-order saddle point on the energy hypersurface for the nucleophilic attack of carbon dioxide on CH3-(CHOH)3-CH3 at the C2 center.Ab initio analytical gradients methods at a 4-31G basis set level are used.The carbon framework and oxygens of the stationary structure superpose with the corresponding atoms of 2-carboxyarabinitol-1,5-biphosphate, which is a transition state analog that has recently been highly refined with X-ray methods. The hydroxyl group in C3 iscis to the C2 oxygen. The C3 center is somewhat pyramidized, the dienol O2-C2-C3-O3 is not planar.The geometry of the transition state allows for simple explanations of both the enolization of Rubisco's substrate ribulose-1,5-biphosphate, O3PO-CH2-CO-(CHOH)2-CH2-OPO3 and oxygenation reaction. The former is due to the pyramidal deformation at C3 and out of plane of O2-C2-C3-O3 framework: the enoliation is intramolecular and is probably enhanced by proton tunnelling. The latter is related with the fact that a rotation around an ethylene-like bond brings the triplet state down in energy. The reactive skeleton has a stationary geometry in the triplet state not very different from the one obtained in the global transition structure. There, the triplet is only 9 kcal/mol above the singlet. The spin densities at C2 and C3 centers clearly indicate the place where oxygenation will take place. 相似文献
5.
Differential Calcium Dependence of γ-Aminobutyric Acid and Acetylcholine Release in Mouse Brain Synaptosomes 总被引:4,自引:3,他引:1
The dependence of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) release on Ca2+ was comparatively studied in synaptosomes from mouse brain, by correlating the influx of 45Ca2+ with the release of the transmitters. It was observed that exposure of synaptosomes to a Na+-free medium notably increases Ca2+ entry, and this condition was used, in addition to K+ depolarization and the Ca2+ ionophore A23187, to stimulate the influx of Ca2+ and the release of labeled GABA and ACh. The effect of ruthenium red (RuR) on these parameters was also investigated. Of the three experimental conditions used, the absence of Na+ in the medium proved to be the most efficient in increasing Ca2+ entry. RuR inhibited by 60-70% the influx of Ca2+ stimulated by K+ depolarization but did not affect its basal influx or its influx stimulated by the absence of Na+ or by A23187. The release of ACh was stimulated by K+ depolarization, absence of Na+ in the medium, and A23187 in a strictly Ca2+-dependent manner, whereas the release of GABA was only partially dependent on the presence of Ca2+ in the medium. The extent of stimulation of ACh release was related to the extent of Ca2+ entry, whereas no such correlation was observed for GABA. In the presence of Na+, RuR did not affect the release of the transmitters induced by A23187. In the absence of Na+, paradoxically RuR notably enhanced the release of both ACh and GABA induced by A23187, in a Ca2+-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
We have evaluated codon usage bias in Drosophila histone genes and have
obtained the nucleotide sequence of a 5,161-bp D. hydei histone gene repeat
unit. This repeat contains genes for all five histone proteins (H1, H2a,
H2b, H3, and H4) and differs from the previously reported one by a second
EcoRI site. These D. hydei repeats have been aligned to each other and to
the 5.0-kb (i.e., long) and 4.8-kb (i.e., short) histone repeat types from
D. melanogaster. In each species, base composition at synonymous sites is
similar to the average genomic composition and approaches that in the small
intergenic spacers of the histone gene repeats. Accumulation of synonymous
changes at synonymous sites after the species diverged is quite high. Both
of these features are consistent with the relatively low codon usage bias
observed in these genes when compared with other Drosophila genes. Thus,
the generalization that abundantly expressed genes in Drosophila have high
codon bias and low rates of silent substitution does not hold for the
histone genes.
相似文献
7.
Neurotoxic Effect of Intranigral Injection of 1-Methyl-4-Phenylpyridinium on GABA-Containing Neurons and Its Relation to Circling Behavior 总被引:1,自引:0,他引:1
Abstract: The ionic species 1-methyl-4-phenylpyridinium (MPP+ ) seems to be the metabolite responsible for the damage to dopaminergic neurons occurring after administration of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In the present study we show that the unilateral stereotaxic microinjection of MPP+ into the substantia nigra pars reticulata in rats produces immediately intense and long-lasting (up to 96 h) contralateral turning behavior in a dose-dependent manner. This behavioral effect was correlated with a dose- and time-dependent decrease (up to 90%) of glutamate decarboxylase activity and with a notable loss of neurons in the injected nigra reticulata. GABA levels in the injected nigra were also decreased, whereas the dopamine concentration in the ipsilateral striatum was not affected at 24 h, when maximal behavioral effects were observed. The circling behavior was prevented by the dopamine carrier blocker nomifensine only during the first 2 h, whereas the dopamine receptor antagonist haloperidol was ineffective. The results indicate that MPP+ is toxic for inhibitory GABAergic neurons in the nigra pars reticulata and, furthermore, suggest that disruption of the function of these GABAergic neurons may be involved in the abnormal motor behavior produced by the injection of MPP+ in the substantia nigra. 相似文献
8.
Abstract— The kinetic behavior of glutamate decarboxylase from mouse brain was analyzed in a wide range of glutamate and pyridoxal 5′-phosphate concentrations, approaching three limit conditions: (I) in the absence of glutamate-pyridoxal phosphate Schiff base; (II) when all glutamate is trapped in the form of Schiff base; (III) when all pyridoxal phosphate is trapped in the form of Schiff base. The experimental results in limit condition (I) are consistent with the existence of two different enzyme activities, one dependent and the other independent of free pyridoxal phosphate. The results obtained in limit conditions (II) and (III) give further support to this postulation. These data show that the free pyridoxal phosphate-dependent activity can be abolished when either all substrate or all cofactor are in the form of Schiff base. The free pyridoxal phosphate-independent activity is also abolished when all substrate is trapped as Schiff base, but it is not affected by the conversion of free pyridoxal phosphate into the Schiff base. A kinetic and mechanistic model for brain glutamate decarboxylase activity, which accounts for these observations as well as for the results of previous dead end-inhibition studies, is postulated. Computer simulations of this model, using the experimentally obtained kinetic constants, reproduced all the observed features of the enzyme behavior. The possible implications of the kinetic model for the regulation of the enzyme activity are discussed. 相似文献
9.
Because previous work showed that in the newborn brain, but not in the adult brain, glutamate decarboxylase (GAD) is notably susceptible to heat, we have studied the possible involvement of GAD inhibition in febrile convulsions and the related changes in gamma-aminobutyric acid (GABA) content. Rats of different ages were subjected to hyperthermia, and GAD activity was determined in brain homogenates by measuring the release of 14CO2 from labeled glutamate and by measuring the formation of GABA. The latter method gave considerably lower values than the former in the youngest rats, and was considered more reliable. With this method, we found a 37-48% inhibition of GAD activity in rat pups 2-5 days old, which showed febrile seizures at progressively higher body temperatures, whereas in 10- and 15-day-old animals, which did not show convulsions, GAD activity was not affected by hyperthermia. Whole-brain GABA levels, however, did not change at any age. In contrast to GAD, choline acetyltransferase and lactic dehydrogenase activities were not altered by hyperthermia at any of the ages studied. These results suggest that a decreased efficiency of the inhibitory neurotransmission mediated by GABA, consequent to the inhibition of GAD activity, may be a factor related to febrile convulsions. 相似文献
10.
Selective Stimulation of Neurotransmitter Release from Chick Retina by Kainic and Glutamic Acids 总被引:10,自引:7,他引:3
The excitatory action of kainic and glutamic acids in chick whole retina was demonstrated as an immediate stimulation of the release of labeled gamma-aminobutyric acid (GABA) and glycine in a superfusion system. This stimulatory effect was 3-10 times greater than that produced by a depolarizing K+ concentration; in addition, it was independent of Ca2+ in the medium, but notably inhibited when Na+ was omitted from the medium. Under identical experimental conditions, neither kainic nor glutamic acid had any effect on the release of labeled dopamine or alpha-aminoisobutyric acid, thus indicating that their effect is not unspecific or due to cell damage. Similar although less marked stimulation of labeled GABA and glycine release by kainic acid was obtained in subcellular retinal fractions, particularly in fraction P1, which contained photoreceptor terminals and outer segments. This stimulation was also Ca2+ independent and greatly reduced when Na+ was omitted from the medium. It is suggested that the stimulation of GABA release by kainic and glutamic acids is probably due to a Na+-dependent, carrier-mediated mechanism that responds to the entry of Na+ produced by the interaction of glutamic and kainic acids with retinal membranes. In cortical or striatal slices from mouse brain, these acids had a negligible stimulatory effect on GABA and dopamine release. 相似文献