全文获取类型
收费全文 | 22254篇 |
免费 | 1529篇 |
国内免费 | 1017篇 |
专业分类
24800篇 |
出版年
2024年 | 54篇 |
2023年 | 301篇 |
2022年 | 633篇 |
2021年 | 1024篇 |
2020年 | 680篇 |
2019年 | 905篇 |
2018年 | 894篇 |
2017年 | 684篇 |
2016年 | 962篇 |
2015年 | 1337篇 |
2014年 | 1518篇 |
2013年 | 1765篇 |
2012年 | 1955篇 |
2011年 | 1826篇 |
2010年 | 1023篇 |
2009年 | 913篇 |
2008年 | 1021篇 |
2007年 | 931篇 |
2006年 | 847篇 |
2005年 | 726篇 |
2004年 | 633篇 |
2003年 | 527篇 |
2002年 | 476篇 |
2001年 | 309篇 |
2000年 | 322篇 |
1999年 | 286篇 |
1998年 | 174篇 |
1997年 | 161篇 |
1996年 | 181篇 |
1995年 | 162篇 |
1994年 | 137篇 |
1993年 | 102篇 |
1992年 | 151篇 |
1991年 | 150篇 |
1990年 | 124篇 |
1989年 | 97篇 |
1988年 | 98篇 |
1987年 | 101篇 |
1986年 | 70篇 |
1985年 | 89篇 |
1984年 | 50篇 |
1983年 | 53篇 |
1982年 | 27篇 |
1981年 | 26篇 |
1980年 | 24篇 |
1979年 | 35篇 |
1978年 | 28篇 |
1977年 | 20篇 |
1975年 | 29篇 |
1974年 | 21篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
102.
We have applied microelectrode technique to record 118 spontaneously firing units from the hypothalamus in rats. Detection of the recording sites showed that 84 were in the paraventricular nucleus (PVN) and 34 were near the PVN (near-PVN). After intracerebroventricular (i.c.v.) administration of atrial natriuretic polypeptide (ANP), 91% (P less than 0.005) of the PVN neurones and 71% (P greater than 0.05) of near-PVN neurones sensitive to ANP showed a significant decrease in spontaneously firing rate. After i.c.v. administration of hypertonic NaCl solution, 64.7% (P less than 0.005) of the PVN neurones and 61.1% (P greater than 0.05) of near-PVN neurones showed a significant increase in firing rate. The results indicate that i.c.v. administration of ANP profoundly inhibits the electrical activity of the PVN neurones, but hypertonic NaCl solution markedly stimulates the PVN neurones. 相似文献
103.
104.
105.
106.
Xuelong Lu Yang Shi Quanlong Lu Yan Ma Jia Luo Qingsong Wang Jianguo Ji Qing Jiang Chuanmao Zhang 《The Journal of biological chemistry》2010,285(43):33281-33293
Lamin B receptor (LBR), a chromatin and lamin B-binding protein in the inner nuclear membrane, has been proposed to target the membrane precursor vesicles to chromatin mediated by importin β during the nuclear envelope (NE) assembly. However, the mechanisms for the binding of LBR with importin β and the membrane targeting by LBR in NE assembly remain largely unknown. In this report, we show that the amino acids (aa) 69–90 of LBR sequences are required to bind with importin β at aa 45–462, and the binding is essential for the NE membrane precursor vesicle targeting to the chromatin during the NE assembly at the end of mitosis. We also show that this binding is cell cycle-regulated and dependent on the phosphorylation of LBR Ser-71 by p34cdc2 kinase. RNAi knockdown of LBR causes the NE assembly failure and abnormal chromatin decondensation of the daughter cell nuclei, leading to the daughter cell death at early G1 phase by apoptosis. Perturbation of the interaction of LBR with importin β by deleting the LBR N-terminal spanning region or aa 69–73 also induces the NE assembly failure, the abnormal chromatin decondensation, and the daughter cell death. The first transmembrane domain of LBR promotes the NE production and expansion, because overexpressing this domain is sufficient to induce membrane overproduction of the NE. Thus, these results demonstrate that LBR targets the membrane precursor vesicles to chromatin by interacting with importin β in a LBR phosphorylation-dependent manner during the NE assembly at the end of mitosis and that the first transmembrane domain of LBR promotes the LBR-bearing membrane production and the NE expansion in interphase. 相似文献
107.
Juhua Yang Yihua Zhu Lu Chen Hongxing Zhang Dinggou Huang Shi Chen Xu Ma 《Biochemical and biophysical research communications》2009,386(4):693-696
We report the clinical and genetic characterization of a Chinese LHON family carrying an ND1/C4171A mutation. This family has high penetrance of visual impairment and extremely low frequency of vision recovery, which is in marked contrast to previously reported results for Korean LHON families with the same mutation. Sequence analysis of the complete mtDNA in the partially defined East Asian haplogroup N9a1 revealed the presence of 29 other variants. A novel heteroplasmic A14841G mutation, one of the variants with a serine substituted for a highly conserved asparagine at amino acid 32 of Cytochrome b (Cytb), may play a synergistic role with the C4171A mutation, leading to significantly different clinical manifestations of LHON among these families. The study further confirmed that C4171A was a rare primary LHON mutation, and the mtDNA background could also contribute to the clinical manifestation of the LHON/C4171A mutation. 相似文献
108.
109.
Differential role of microenvironment in microencapsulation for improved cell tolerance to stress 总被引:6,自引:0,他引:6
Sun ZJ Lv GJ Li SY Yu WT Wang W Xie YB Ma X 《Applied microbiology and biotechnology》2007,75(6):1419-1427
The effect of the microenvironment in alginate–chitosan–alginate (ACA) microcapsules with liquid core (LCM) and solid core
(SCM) on the physiology and stress tolerance of Sacchromyces cerevisiae was studied. The suspended cells were used as control. Cells cultured in liquid core microcapsules showed a nearly twofold
increase in the intracellular glycerol content, trehalose content, and the superoxide dismutase (SOD) activity, which are
stress tolerance substances, while SCM did not cause the significant physiological variation. In accordance with the physiological
modification after being challenged with osmotic stress (NaCl), oxidative stress (H2O2), ethanol stress, and heat shock stress, the cell survival in LCM was increased. However, SCM can only protect the cells
from damaging under ethanol stress. Cells released from LCM were more resistant to hyperosmotic stress, oxidative stress,
and heat shock stress than cells liberated from SCM. Based on reasonable analysis, a method was established to estimate the
effect of microenvironment of LCM and SCM on the protection of cells against stress factors. It was found that the resistance
of LCM to hyperosmotic stress, oxidative stress, and heat shock stress mainly depend on the domestication effect of LCM’s
microenvironment. The physical barrier of LCM constituted by alginate–chitosan membrane and liquid alginate matrix separated
the cells from the damage of oxidative stress and ethanol stress. The significant tolerance against ethanol stress of SCM
attributed to the physical barrier consists of solid alginate–calcium matrix and alginate–chitosan membrane. 相似文献
110.
Chronic ethanol exposure of human pancreatic normal ductal epithelial cells induces cancer stem cell phenotype through SATB2 下载免费PDF全文
Wei Yu Yuming Ma Sharmila Shankar Rakesh K. Srivastava 《Journal of cellular and molecular medicine》2018,22(8):3920-3928
The incidence of pancreatic cancer is on the rise. Risk factors for pancreatic cancer include alcohol toxicity and metabolic conditions such as obesity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes. However, the molecular mechanism by which chronic alcohol consumption contributes to pancreatic cancer is not well understood. The purpose of the study was to demonstrate the effects of long‐term chronic ethanol exposure on the transformation of human pancreatic normal ductal epithelial (HPNE) cells. Our data showed that ethanol‐transformed HPNE cells were more progressively transformed exhibiting spheroids and colonies, and anchorage‐independent growth. These transformed cells contained high levels of reactive oxygen species and induced SATB2 expression. Furthermore, during ethanol‐induced cellular transformation, cells gained the phenotypes of cancer stem cells (CSCs) by expressing pluripotency maintaining factors (Oct4, Sox2, cMyc and KLF4) and stem cell markers (CD24, CD44 and CD133). Ethanol‐induced SATB2 can bind to the promoters of KLF4, Oct4, cMyc, Sox2, Bcl‐2 and XIAP genes. Suppression of SATB2 expression in ethanol‐transformed HPNE cells inhibited cell proliferation, colony formation and markers of CSCs and pluripotency. These data suggest that chronic alcohol consumption may contribute toward the development of pancreatic cancer by converting HPNE cells to cancer stem‐like cells. 相似文献