全文获取类型
收费全文 | 2234篇 |
免费 | 102篇 |
国内免费 | 33篇 |
出版年
2023年 | 16篇 |
2022年 | 19篇 |
2021年 | 45篇 |
2020年 | 44篇 |
2019年 | 42篇 |
2018年 | 38篇 |
2017年 | 24篇 |
2016年 | 38篇 |
2015年 | 58篇 |
2014年 | 89篇 |
2013年 | 126篇 |
2012年 | 84篇 |
2011年 | 99篇 |
2010年 | 79篇 |
2009年 | 90篇 |
2008年 | 122篇 |
2007年 | 108篇 |
2006年 | 109篇 |
2005年 | 105篇 |
2004年 | 119篇 |
2003年 | 101篇 |
2002年 | 111篇 |
2001年 | 103篇 |
2000年 | 54篇 |
1999年 | 54篇 |
1998年 | 47篇 |
1997年 | 38篇 |
1996年 | 40篇 |
1995年 | 50篇 |
1994年 | 53篇 |
1993年 | 26篇 |
1992年 | 33篇 |
1991年 | 18篇 |
1990年 | 11篇 |
1989年 | 28篇 |
1988年 | 18篇 |
1987年 | 16篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1981年 | 12篇 |
1980年 | 10篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 7篇 |
排序方式: 共有2369条查询结果,搜索用时 15 毫秒
1.
Abstract: In primary cultures of rat cerebellar granule neurons, GABA treatment (50 μ M , 7 days) caused a withdrawal supersensitivity selective for the metabotropic glutamate receptors that mainly prefer l -glutamate, quisqua- late and, to a lesser extent, kainate. The withdrawal supersensitivity was absent when 10 μ M SR-95531 was coadministered with GABA during the treatment period, an event that suggests the GABAA receptors primarily produced the GABA treatment effect. This was supported further by the inability of baclofen treatment to mimic completely the treatment effect of GABA. Withdrawal from 7 days of baclofen treatment only produced a slight increase in the metabotropic effect of l -glutamate and carbachol. In addition, in untreated neurons, baclofen had no acute effect, whereas GABA inhibited the effect of l -glutamate and carbachol. The inhibitory effect of GABA was reversed by SR-95531 and was absent in neurons treated with GABA. These observations suggest the involvement of GABAA receptors and the apparent development of tolerance to GABA, respectively. Also, dependence on GABA may have occurred; the metabotropic effects of glutamate, kainate, and quisqualate were not altered in neurons maintained with GABA treatment. 相似文献
2.
Mario Stampanoni Bassi Tommaso Nuzzo Luana Gilio Mattia Miroballo Alessia Casamassa Fabio Buttari Paolo Bellantonio Roberta Fantozzi Giovanni Galifi Roberto Furlan Annamaria Finardi Arianna De Rosa Anna Di Maio Francesco Errico Diego Centonze Alessandro Usiello 《Journal of neurochemistry》2021,159(5):857-866
3.
4.
5.
B. T. Baune T. Suslow C. Beśte E. Birosova K. Domschke C. Sehlmeyer C. Konrad 《Genes, Brain & Behavior》2010,9(5):459-466
Set‐shifting and maintenance are complex cognitive processes, which are often impaired in schizophrenia. The genetic basis of these processes is poorly understood. We aimed to investigate the association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set‐shifting in healthy individuals. The relationship between 14 selected single nucleotide polymorphisms (SNPs) of the GRM3 gene and cognitive set‐shifting as measured by perseverative errors using the modified card sorting test (MCST) was analysed in a sample of N = 98 young healthy individuals (mean age in years: 22.7 ± 0.19). Results show that SNP rs17676277 is related to the performance on the MCST. Subjects with the TT genotype showed significantly less perseverative errors as compared with the AA (P = 0.025) and AT (P = 0.0005) and combined AA/AT genotypes (P = 0.0005). Haplotype analyses suggest the involvement of various SNPs of the GRM3 gene in perseverative error processing in a dominant model of inheritance. The findings strongly suggest that the genetic variation (rs17676277 and three haplotypes) in the metabotropic GRM3 is related to cognitive set‐shifting in healthy individuals independent of working memory. However, because of a relatively small sample size for a genetic association study, the present results are tentative and require replication. 相似文献
6.
Although the amino acid glutamate is used as an intercellular signaling molecule for normal bone homeostasis, little is known regarding its possible role in the metabolic disruption characteristic of bone metastasis. We have previously shown in vitro that cancer cell lines relevant to bone metastasis release glutamate into the extracellular environment. This study demonstrates the expression of multiple glutamate transporters in cancer cell lines of non-central nervous system origin. Furthermore, we identify the molecular mechanism responsible for glutamate export and show that this system can be inhibited pharmacologically. By highlighting that glutamate secretion is a common biological feature of cancer cells, this study suggests that tumor-derived glutamate could interfere with glutamate-dependent intercellular signaling in normal bone. Pharmacological interference with cancer cell glutamate release may be a viable option for limiting host bone response to invading tumor cells in bone metastasis. 相似文献
7.
8.
9.
Yao Shen Yueyang Tian Xiaojie Shi Jianbo Yang Li Ouyang Jieqiong Gao Jianxin Lu 《Cell biochemistry and function》2014,32(6):530-537
Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate‐induced gliotoxicity. Exposure to 10‐mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non‐mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP‐linked respiration of astrocytes was reduced. The glutamate‐induced astrocyte damage can be mimicked by the non‐metabolized substrate d ‐aspartate but reversed by the non‐selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate‐induced gliotoxicity in cortical astrocytes. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
10.
Lili Guo Alexander A. Shestov Andrew J. Worth Kavindra Nath David S. Nelson Dennis B. Leeper Jerry D. Glickson Ian A. Blair 《The Journal of biological chemistry》2016,291(1):42-57
The antitumor agent lonidamine (LND; 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid) is known to interfere with energy-yielding processes in cancer cells. However, the effect of LND on central energy metabolism has never been fully characterized. In this study, we report that a significant amount of succinate is accumulated in LND-treated cells. LND inhibits the formation of fumarate and malate and suppresses succinate-induced respiration of isolated mitochondria. Utilizing biochemical assays, we determined that LND inhibits the succinate-ubiquinone reductase activity of respiratory complex II without fully blocking succinate dehydrogenase activity. LND also induces cellular reactive oxygen species through complex II, which reduced the viability of the DB-1 melanoma cell line. The ability of LND to promote cell death was potentiated by its suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation. Using stable isotope tracers in combination with isotopologue analysis, we showed that LND increased glutaminolysis but decreased reductive carboxylation of glutamine-derived α-ketoglutarate. Our findings on the previously uncharacterized effects of LND may provide potential combinational therapeutic approaches for targeting cancer metabolism. 相似文献