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排序方式: 共有940条查询结果,搜索用时 140 毫秒
1.
2.
A Schousboe 《Neurochemistry international》1999,34(5):373-377
Cerebellar granule neurons can be conveniently kept in culture. They constitute a useful model to study regulation of glutamatergic activity, in particular the inhibitory action of GABA (7-aminobutyrate). GABA exerts an inhibitory action on evoked transmitter release acting on both GABA(A) and GABA(B) receptors. The functional properties of these receptors are dependent upon the environment of the neurons during early development in culture as the expression of both receptor subtypes is enhanced by exposure of the neurons to GABA(A) receptor agonists. Thus, the inducible GABA(A) receptors are of low affinity and lack benzodiazepine sensitivity, and the G-protein coupling differs among the native and the inducible GABA(B) receptors. Moreover, the GABA(A) and the GABA(B) receptors are functionally coupled, leading to a disinhibitory action of GABA. Therefore drugs exhibiting selective agonist or antagonist action on subclasses of GABA(A) and GABA(B) may be of potential use as regulators of glutamatergic excitatory activity. 相似文献
3.
Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT) exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF) is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12) and compared them with placenta from depressed (n = 12) and healthy mothers (n = 12). Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the clinical relevance of our findings still needs to be investigated. 相似文献
4.
Ulrik Pedersen-Bjergaard Lars B geskov Nielsen Kai Jensen Lars Edvinsson Inger Jansen Jes Olesen 《Peptides》1989,10(6):1147-1152
Neurokinin A (NKA), substance P (SP) and the two peptides combined (SP + NKA) were injected intracutaneously on the forearm and into the temporal muscle of healthy volunteers. Pain intensity, cutaneous wheal and flare responses and tenderness of the temporal muscle were quantitated. SP but not NKA induced cutaneous pain. This relates the algesic effect of SP to the specific N-terminal amino acid sequence of the peptide, not shared by NKA. NKA, however, potentiated the algesic effect of SP as SP + NKA induced a significantly prolonged cutaneous pain sensation. Both peptides induced wheals, but only SP induced flare. These results confirm previous studies relating wheal formation to the identical C-terminal amino acid sequence of the two peptides and flare reaction to the N-terminal part of SP. Injections into the temporal muscle did not cause pain or tenderness. 相似文献
5.
The enzymatic mechanism and the kinetic parameters of GABA-transaminase extracted from cultured mouse cerebral cortex neurons and astrocytes were studied. Neuronal as well as astrocytic GABA-transaminase obeyed a bi bi ping-pong reaction mechanism. The estimated Km-values for -ketoglutarate and GABA were significantly lower for astroglial GABA-transaminase compared to the neuronal enzyme suggesting a possible existence of cell specific isozymes of GABA-transaminase. The observed enzymatic mechanism and the magnitude of the estimated kinetic parameters imply that GABA-transaminase synthesized in the two types of cultured neural cells is mechanistically and kinetically equivalent to the enzyme synthesized in the brainin vivo. 相似文献
6.
Energy metabolism in glutamatergic neurons,GABAergic neurons and astrocytes in primary cultures 总被引:9,自引:0,他引:9
Several aspects of energy metabolism (glucose utilization, lactate production,14CO2 production from labeled glucose, glutamate or pyruvate, oxygen consumption and contents of ATP and phosphocreatine) were measured in cerebellar granule cells (glutamatergic) in primary cultures and compared with corresponding data for cerebral cortical neurons (mainly GABA-ergic) and astrocytes. Cerebellar granule cells and astrocytes were metabolically more active than cerebral cortical neurons. Glutamate which is utilized as a major metabolic fuel as astrocytes and, to a lesser extent, in cerebral cortical neurons, was virtually not oxidized in cerebellar granule cells.Special Issue dedicated to Prof. Holger Hydén. 相似文献
7.
Mice were injected intramuscularly (2 mmol/kg) with the glia-selective GABA uptake inhibitor 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) 60 min prior to sacrifice, or with glycine (10 mmol/kg) 45 min before death, or with a combination of both. After decapitation of the animals, the brains were removed and synaptosomes prepared and analyzed for content of GABA, taurine, glutamine, serine, glutamate and aspartate. While no differences as compared with control animals were found for aspartate, serine and glutamine, synaptosomal GABA levels were increased significantly after injections with either THPO or glycine. The individual effects of THPO and glycine were found to be additive. Taurine levels were decreased to a similar extent in animals which had received either THPO alone or THPO in conjunction with glycine. Treatment with THPO and glycine in combination led to a decrease in the synaptosomal glutamate content. The findings are consistent with the previously observed synergistic anticonvulsant actions of THPO and glycine being mediated via the GABA neurotransmitter system. 相似文献
8.
Alpha-ketoglutarate together with an amino group donor (alanine) was shown to be able to serve as a precursor for the glutamate pool which is released by potassium-induced depolarization (i.e., transmitter glutamate) in cerebellar granule cells. However, these compounds could not be utilized as precursors for intracellular glutamate or for release of transmitter aspartate. The formation of transmitter glutamate was inhibited by the transamination inhibitor aminooxyacetic acid but not by phenylsuccinate, an inhibitor of the dicarboxylate carrier in the mitochondrial membrane. Both of these inhibitors have previously been found to inhibit synthesis of transmitter glutamate from glutamine. The results support the hypothesis that alpha-ketoglutarate and alanine undergo transamination in the cytosol to form pyruvate and glutamate, and that this glutamate pool is available for transmitter release of glutamate but does not constitute the major intracellular pool of glutamate. 相似文献
9.
Niels Westergaard Ursula Sonnewald Steffen B. Petersen Arne Schousboe 《Neurochemical research》1991,16(8):919-923
In the present investigation a method is described for culturing cerebellar granule cells (glutamatergic neurons), cerebral cortical neurons (GABAergic neurons) and cortical astrocytes on Cytodex 3 microcarriers. It was possible to obtain a high yield of attached neurons and astrocytes on the microcarriers and the cell specific characteristics such as the ability to release neurotransmitter (neurons) and a high activity of glutamine synthetase (astrocytes) were preserved. This system, allowing mixtures of neurons and astrocytes at any given ratio to be produced, may constitute an attractive model system by which the interaction between neurons and astrocytes with regard to exchange of neurotransmitter precursors as well as other compounds may be studied. 相似文献
10.
Inositolphospholipid-accelerated activation of prekallikrein by activated factor XII and its inhibition by beta 2-glycoprotein I 总被引:3,自引:0,他引:3
I Schousboe 《European journal of biochemistry》1988,176(3):629-636
Inositolphospholipid-accelerated activation of prekallikrein by alpha-factor XIIa was determined by measuring the appearance of kallikrein amidolytic activity towards the chromogenic substrate, D-prolyl-phenylalanyl-arginyl p-nitroanilide (S-2302). The activation reaction did not exhibit normal Michaelis-Menten kinetics. The Hill coefficient was found to be 1.6 indicating that the activation followed an allosteric reaction mechanism. The temperature dependence of the reaction showed a thermal transition at 30 degrees C, which in addition to the allosteric reaction mechanism is indicative of a conformational change of prekallikrein following binding to the inositolphospholipid. The reaction exhibited pH optimum at pH 7.2 and ionic strength optimum at 50 mM NaCl. At optimal conditions the apparent KA value and the kcat/KA value for factor XIIa on prekallikrein were calculated to be 73 nM and 9.3 x 10(6) s-1 M-1, respectively. Kinetic constants could not be calculated at salt concentrations higher than the optimal concentrations, as Lineweaver-Burk plots were curvilinear in agreement with the Hill coefficient greater than unity. The activation was inhibited competitively by beta 2-glycoprotein I with a Ki value of 77 nM as determined by the Dixon plot. 相似文献