全文获取类型
收费全文 | 977篇 |
免费 | 99篇 |
国内免费 | 33篇 |
出版年
2024年 | 27篇 |
2023年 | 9篇 |
2022年 | 14篇 |
2021年 | 10篇 |
2020年 | 51篇 |
2019年 | 46篇 |
2018年 | 43篇 |
2017年 | 41篇 |
2016年 | 20篇 |
2015年 | 20篇 |
2014年 | 52篇 |
2013年 | 77篇 |
2012年 | 51篇 |
2011年 | 47篇 |
2010年 | 27篇 |
2009年 | 46篇 |
2008年 | 42篇 |
2007年 | 50篇 |
2006年 | 32篇 |
2005年 | 30篇 |
2004年 | 20篇 |
2003年 | 22篇 |
2002年 | 15篇 |
2001年 | 22篇 |
2000年 | 15篇 |
1999年 | 16篇 |
1998年 | 18篇 |
1997年 | 17篇 |
1996年 | 24篇 |
1995年 | 15篇 |
1994年 | 18篇 |
1993年 | 16篇 |
1992年 | 13篇 |
1991年 | 13篇 |
1990年 | 16篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 14篇 |
1986年 | 12篇 |
1985年 | 12篇 |
1984年 | 14篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1975年 | 4篇 |
1974年 | 1篇 |
1973年 | 4篇 |
排序方式: 共有1109条查询结果,搜索用时 15 毫秒
91.
香蕉一个Ⅲ类酸性几丁质酶基因与果实成熟关系的研究 总被引:2,自引:0,他引:2
为了解Ⅲ类酸性几丁质酶基因(MaCHⅢ)与香蕉果实采后成熟过程的相互关系,对经乙烯和1-甲基环丙烯(1-MCP)处理的巴西香蕉果实采后乙烯释放量、Ⅲ类酸性几丁质酶基因(MaCHⅢ)表达以及几丁质酶活性进行了测定.结果显示:(1)乙烯催熟处理的香蕉果实,乙烯释放量比对照处理的果实提前15 d达到高峰;1-MCP处理的香蕉果实,乙烯生物合成和果实成熟明显受到了抑制.(2)外源乙烯加速了MaCHⅢ基因的下调表达和Ⅲ类酸性几丁质酶活性的下降,MaCHⅢ表达量和Ⅲ类酸性几丁质酶活性分别在采后第3天和第4天下降到最小值.(3)1-MCP处理使MaCHⅢ基因呈现上调表达,Ⅲ类酸性几丁质酶活性上升,MaCHⅢ基因表达量和Ⅲ类酸性几丁质酶活性分别在采后18 d和25 d达到高峰.研究表明,MaCHⅢ基因可能与香蕉果实采后成熟呈负相关. 相似文献
92.
Kosman J Carmean N Leaf EM Dyamenahalli K Bassuk JA 《Journal of molecular biology》2007,371(4):883-901
SPARC (secreted protein acidic and rich in cysteine), although primarily known as a secreted, matricellular protein, has also been identified in urothelial cell nuclei. Many biological activities, including inhibition of cell adhesion and repression of DNA synthesis, have been ascribed to SPARC, but the influence of its intracellular localization on each of these activities is unknown. When exposed by epitope retrieval and nuclear matrix unmasking techniques, endogenous SPARC was found to localize strongly to the nuclei and the nuclear matrix of cultured urothelial cells. Live-cell time-lapse imaging revealed that exogenous fluorescently labeled recombinant (r) SPARC was taken up from medium over a 16 h period and accumulated inside cells. Two variants of rSPARC with alterations in its putative nuclear localization signal (NLS) were generated to investigate the existence and effects of the NLS. These variants demonstrated similar biophysical characteristics as the wild-type protein. Visualization by a variety of techniques, including live-cell imaging, deconvolution microscopy, and cell fractionation, all concurred that exogenous rSPARC was not able to localize to cell nuclei, but instead accumulated as perinuclear clusters. Localization of the rSPARC NLS variants was no different than wild-type, arguing against the presence of an active NLS in rSPARC. Imaging experiments showed that only permeabilized, dead cells avidly took up rSPARC into their nuclei. The rSPARC(no NLS) variant proved ineffective at inhibiting DNA synthesis, whereas the rSPARC(strong NLS) variant was a more potent inhibitor of DNA synthesis than was wild-type rSPARC. The motif of SPARC that inhibits the synthesis of urothelial cell DNA is therefore not a nuclear localization signal, but its manipulation holds therapeutic potential to generate a "Super-SPARC" that can quiesce proliferative tissues. 相似文献
93.
The omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA, 22:6n-3) has been previously shown to facilitate some of the vital functions of astrocytes. Since some dietary oils contain alpha-linolenic acid (ALA, 18:3n-3), which is a precursor of DHA, we examined their effect on astrocyte development. Fatty acids (FAs) were isolated from commonly used oils and their compositions were determined by GLC. FAs from three oils, viz. coconut, mustard and linseed were studied for their effect on astrocyte morphology. Parallel studies were conducted with FAs from the same oils after heating for 72 h. Unlike coconut oil, FAs from mustard and linseed, both heated and raw, caused significant morphogenesis of astrocytes in culture. ss-AR binding was also substantially increased in astrocytes treated with FAs from raw mustard and linseed oils as compared to astrocytes grown in normal medium. The expression profile of the isoforms of GFAP showed that astrocyte maturation by FAs of mustard and linseed oil was associated with appearance of acidic variants of GFAP and disappearance of some neutral isoforms similar to that observed in cultures grown in serum containing medium or in the presence of DHA. Taken together, the study highlights the contribution of specific dietary oils in facilitating astrocyte development that can have potential impact on human health. 相似文献
94.
Yamaguchi H Zhu J Yu T Sasaki K Umetsu H Kidachi Y Ryoyama K 《Cell biology international》2007,31(6):638-644
95.
Burbaeva GSh Boksha IS Tereshkina EB Savushkina OK Starodubtseva LI Turishcheva MS Mukaetova-Ladinska E 《Neurochemical research》2007,32(9):1434-1444
We have used a systemic approach to establish a relationship between enzyme measures of glial glutamate and energy metabolism
(glutamine synthetase and glutamine synthetase-like protein, glutamate dehydrogenase isoenzymes, brain isoform creatine phosphokinase)
and two major glial proteins (glial fibrillary acidic protein and myelin basic protein) in autopsied brain samples taken from
patients with schizophrenia (SCH) and mentally healthy subjects (23 and 22 cases, respectively). These biochemical parameters
were measured in tissue extracts in three brain areas (prefrontal cortex, caudate nucleus, and cerebellum). Significant differences
in the level of at least one of the glutamate metabolizing enzymes were observed between two studied groups in all studied
brain areas. Different patterns of correlative links between the biochemical parameters were found in healthy and schizophrenic
brains. These findings give a new perspective to our understanding of the impaired regulation of enzyme levels in the brain
in SCH. 相似文献
96.
Kuo CC Liu TW Chen LT Shiah HS Wu CM Cheng YT Pan WY Liu JF Chen KL Yang YN Chen SN Chang JY 《Free radical biology & medicine》2011,51(12):2195-2209
Arsenic trioxide (As2O3) is an effective treatment for relapsed or refractory acute promyelocytic leukemia (APL). After the discovery of As2O3 as a promising treatment for APL, several studies investigated the use of As2O3 as a single agent in the treatment of solid tumors; however, its therapeutic efficacy is limited. Thus, the systematic study of the combination of As2O3 with other clinically used chemotherapeutic drugs to improve its therapeutic efficacy in treating human solid tumors is merited. In this study, we demonstrate for the first time, using isobologram analysis, that As2O3 exhibits a synergistic interaction with N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU). The synergistic augmentation of the cytotoxicity of As2O3 with BCNU is in part through the autophagic cell death machinery in human solid tumor cells. As2O3 and BCNU in combination produce enhanced cytotoxicity via the depletion of reduced glutathione (GSH) and augmentation of reaction oxygen species (ROS) production. Further analysis indicated that the extension of GSH depletion by this combined regimen occurs through the inhibition of the catalytic activity of glutathione reductase. Blocking ROS production with antioxidants or ROS scavengers effectively inhibits cell death and autophagy formation, indicating that redox-mediated autophagic cell death involves the synergism of As2O3 with BCNU. Taken together, this is the first evidence that BCNU could help to extend the therapeutic spectrum of As2O3. These findings will be useful in designing future clinical trials of combination chemotherapy with As2O3 and BCNU, with the potential for broad use against a variety of solid tumors. 相似文献
97.
98.
99.
Among the first reported functions of 14-3-3 proteins was the regulation of tyrosine hydroxylase (TH) activity suggesting a possible involvement of 14-3-3 proteins in Parkinson's disease. Since then the relevance of 14-3-3 proteins in the pathogenesis of chronic as well as acute neurodegenerative diseases, including Alzheimer's disease, polyglutamine diseases, amyotrophic lateral sclerosis and stroke has been recognized. The reported function of 14-3-3 proteins in this context are as diverse as the mechanism involved in neurodegeneration, reaching from basal cellular processes like apoptosis, over involvement in features common to many neurodegenerative diseases, like protein stabilization and aggregation, to very specific processes responsible for the selective vulnerability of cellular populations in single neurodegenerative diseases.Here, we review what is currently known of the function of 14-3-3 proteins in nervous tissue focussing on the properties of 14-3-3 proteins important in neurodegenerative disease pathogenesis. 相似文献
100.
Hjelmeland AB Wu Q Heddleston JM Choudhary GS MacSwords J Lathia JD McLendon R Lindner D Sloan A Rich JN 《Cell death and differentiation》2011,18(5):829-840
Malignant gliomas are lethal cancers that display cellular hierarchies with cancer stem cells at the apex. Glioma stem cells (GSCs) are not uniformly distributed, but rather located in specialized niches, suggesting that the cancer stem cell phenotype is regulated by the tumor microenvironment. Indeed, recent studies show that hypoxia and its molecular responses regulate cancer stem cell maintenance. We now demonstrate that acidic conditions, independent of restricted oxygen, promote the expression of GSC markers, self-renewal and tumor growth. GSCs exert paracrine effects on tumor growth through elaboration of angiogenic factors, and low pH conditions augment this expression associated with induction of hypoxia inducible factor 2α (HIF2α), a GSC-specific regulator. Induction of HIF2α and other GSC markers by acidic stress can be reverted by elevating pH in vitro, suggesting that raising intratumoral pH may be beneficial for targeting the GSC phenotype. Together, our results suggest that exposure to low pH promotes malignancy through the induction of a cancer stem cell phenotype, and that culturing cancer cells at lower pH reflective of endogenous tumor conditions may better retain the cellular heterogeneity found in tumors. 相似文献