全文获取类型
收费全文 | 19578篇 |
免费 | 1782篇 |
国内免费 | 3125篇 |
出版年
2024年 | 85篇 |
2023年 | 351篇 |
2022年 | 798篇 |
2021年 | 1202篇 |
2020年 | 949篇 |
2019年 | 1048篇 |
2018年 | 917篇 |
2017年 | 678篇 |
2016年 | 956篇 |
2015年 | 1434篇 |
2014年 | 1659篇 |
2013年 | 1730篇 |
2012年 | 2122篇 |
2011年 | 1858篇 |
2010年 | 1147篇 |
2009年 | 1078篇 |
2008年 | 1164篇 |
2007年 | 954篇 |
2006年 | 851篇 |
2005年 | 697篇 |
2004年 | 543篇 |
2003年 | 504篇 |
2002年 | 377篇 |
2001年 | 232篇 |
2000年 | 211篇 |
1999年 | 198篇 |
1998年 | 114篇 |
1997年 | 80篇 |
1996年 | 82篇 |
1995年 | 83篇 |
1994年 | 53篇 |
1993年 | 42篇 |
1992年 | 54篇 |
1991年 | 49篇 |
1990年 | 30篇 |
1989年 | 32篇 |
1988年 | 16篇 |
1987年 | 20篇 |
1986年 | 15篇 |
1985年 | 14篇 |
1984年 | 11篇 |
1983年 | 11篇 |
1982年 | 13篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1974年 | 3篇 |
1971年 | 1篇 |
1966年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Thomas J. Thekkumkara Jing Du John C. Zwaagstra Kathleen M. Conrad John Krupinski Kenneth M. Baker 《Molecular and cellular biochemistry》1995,152(1):77-86
G-protein coupled Angiotensin II receptors (AT1A), mediate cellular responses through multiple signal transduction pathways. In AT1A receptor-transfected CHO-K1 cells (T3CHO/AT1A), angiotensin II (AII) stimulated a dose-dependent (EC50=3.3 nM) increase in cAMP accumulation, which was inhibited by the selective AT1, nonpeptide receptor antagonist EXP3174. Activation of protein kinase C, or increasing intracellular Ca2+ with ATP, the calcium ionophore A23187 or ionomycin failed to stimulate cAMP accumulation. Thus, AII-induced cAMP accumulation was not secondary to activation of a protein kinase C- or Ca2+/calmodulin-dependent pathway. Since cAMP has an established role in cellular growth responses, we investigated the effect of the AII-mediated increase in cAMP on cell number and [3H]thymidine incorporation in T3CHOA/AT1A cells. AII (1 M) significantly inhibited cell number (51% at 96 h) and [3H]thymidine incorporation (68% at 24 h) compared to vehicle controls. These effects were blocked by EXP3174, confirming that these responses were mediated through the AT1 receptor. Forskolin (10 M) and the cAMP analog dibutyryl-cAMP (1 mM) also inhibited [3H]thymidine incorporation by 55 and 25% respectively. We extended our investigation on the effect of AII-stimulated increases in cAMP, to determine the role for established growth related signaling events, i.e., mitogen-activated protein kinase activity and tyrosine phosphorylation of cellular proteins. AII-stimulated mitogen-activated protein kinase activity and phosphorylation of the 42 and 44 kD forms. These events were unaffected by forskolin stimulated increases in cAMP, thus the AII-stimulated mitogen-activated protein kinase activity was independent of cAMP in these cells. AII also stimulated tyrosine phosphorylation of a number of cellular proteins in T3CHO/AT1A cells, in particular a 127 kD protein. The phosphorylation of the 127 kD protein was transient, reaching a maximum at 1 min, and returning to basal levels within 10 min. The dephosphorylation of this protein was blocked by a selective inhibitor of cAMP dependent protein kinase A, H89-dihydrochloride and preexposure to forskolin prevented the AII-induced transient tyrosine phosphorylation of the 127 kD protein. These data suggest that cAMP, and therefore protein kinase A can contribute to AII-mediated growth inhibition by stimulating the dephosphorylation of substrates that are tyrosine phosphorylated in response to AII. 相似文献
102.
One- and two-dimensional gel electrophoresis were employed to characterise the proteins derived from the ribosomes of the thermophilic fungusThermomyces lanuginosus. Approximately 32 (29 basic and 3 acidic) and 45 (43 basic and 2 acidic) protein spots were resolved fromTh. lanuginosus small and large ribosomal subunits, respectively. The molecular weight of the small subunit proteins ranged from 9,800–36,000 Da with a number average molecular weight of 20,300 Da. The molecular weight range for the large subunit proteins was 12,000–48,500 Da with a number average molecular weight of 25,900 Da. Most proteins appeared to be present in unimolar amounts. These data are comparable with but not identical to those from other eukaryotic ribosomes. The sensitivities of the ribosomal proteins to increasing concentrations of NH4Cl were also evaluated by two-dimensional gel electrophoresis. Most ribosomal proteins were gradually released over a wide range of salt concentrations but some were preferentially enriched in one or two salt conditions. 相似文献
103.
Characterization of Calpain-Mediated Proteolysis of GluR1 Subunits of α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionate Receptors in Rat Brain 总被引:1,自引:0,他引:1
Xiaoning Bi Jing Chen Sandeeb Dang Robert J. Wenthold Georges Tocco Michel Baudry 《Journal of neurochemistry》1997,68(4):1484-1494
Abstract: Previous results have indicated that GluR1 subunits of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are targets of calpain. In the present study, we determined the effects of calpain treatment of synaptic membranes on GluR1 subunits using western blots with antibodies directed against the C-terminal (C-Ab) and the N-terminal (N-Ab) domains of the proteins, and compared them with the effects of calcium treatment of frozen-thawed brain sections. Calpain treatment of synaptic membranes resulted in a large decrease in the GluR1 band (105 kDa) labeled with C-Ab and in the formation of a doublet band labeled with N-Ab due to the appearance of a new species of GluR1 (98 kDa). These effects were blocked almost completely by calpain inhibitors. Calpain-induced changes in GluR1 immunological properties were not associated with modifications of [3 H]AMPA or 6-cyano-7-[3 H]nitroquinoxaline-2,3-dione ([3 H]CNQX) binding. Treatment of frozen-thawed brain sections with concentrations of calcium as low as 0.2 m M resulted in a large decrease in the 105-kDa GluR1 band and in the concurrent appearance of the 98-kDa band. This treatment was associated with increased [3 H]AMPA and [3 H]CNQX binding. These results suggest that there exist several types/states of GluR1 subunits exhibiting different sensitivities to calpain. Our data also indicate the existence of additional calcium-dependent processes regulating the characteristics of receptors in intact tissues. 相似文献
104.
105.
以克山病病区粮配成基础饲料,另在基础饲料中分别补充Se或VE,或Se+VE喂养大鼠,在细胞及亚细胞水平上以Ca代谢为主研究并比较了Se和VE在克山病病因中的作用。测量了心肌细胞和心肌线粒体的Ca代谢及有关指标、心肌线粒体能量转换功能及心肌组织自由基含量。结果表明,在低Se病区粮中补充Se或VE均能在一定程度上预防病区粮中致病因素对心肌细胞及线粒体的损伤;并且补充Se或VE均能使心肌组织中自由基含量减少。提示Se和VE是通过清除体内过量自由基预防细胞和线粒体的损伤的。但值得注意的是,实验中所用病区粮VE含量不低于甚至高于非病区对照粮,在低Se情况下,所补VE的量需要相当大(如本实验中补充200μg/g)才能较明显地预防心肌细胞和心肌线粒体的损伤。通过对这些结果的分析,进一步肯定低Se是克山病形成的重要因素之一。 相似文献
106.
107.
以模式植物拟南芥(Arabidopsis thaliana(L.)Heynh)为材料,从生理及分子层面研究碳量子点(Carbon quantum dots,CQDs)对拟南芥生物效应的影响。结果显示,CQDs能被拟南芥根部吸收并连续运输到叶片,对种子萌发率无明显影响,但能显著促进幼苗主根伸长和株重的增加。幼苗叶片叶绿体中色素含量随CQDs浓度的升高而显著降低。脯氨酸与丙二醛含量随CQDs浓度的升高呈先上升后下降趋势。超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性随CQDs浓度的升高呈先上升后下降趋势,在抗氧化酶系统中起主导作用;叶片内源过氧化氢(H2O2)的积累随CQDs浓度的升高而升高,具有显著的浓度依赖效应。与其他纳米材料处理不一样的是,硫同化及胁迫相关基因在CQDs处理后表达量下调,这可能与CQDs粒子本身的特性有关。 相似文献
108.
基于11个内陆居群和32个岛屿居群的252份标本,采用ISSR分子标记技术对真藓(Bryum argenteum Hedw.)的遗传多样性进行了研究。结果显示:岛屿与内陆居群间的遗传多样性差异显著,岛屿居群间的分化程度(Gst=0.453)大于内陆居群(Gst=0.387),岛屿居群的遗传分化与地理来源间存在极显著相关性(r=0.478,n=175,P<0.001)。地理隔离效应是导致岛屿居群间遗传分化的重要因素。岛内居群间的遗传分化水平较低,仅有29.4%~29.7%的遗传多样性存在于居群间。聚类分析表明,43个居群可划分为10大类群,真藓遗传关系受地理因素和生境异质性的影响,水域隔离影响了真藓繁殖体在岛屿间的传播。 相似文献
109.
本文用中空纤维柱超滤浓缩尿,再经离子交换层析、聚焦层析、凝胶过滤和制备型聚丙烯酰胺凝胶电泳(PAGE)-层析等四步从15L再生障碍性贫血患者尿中获得约2mg EPO制品。比活性达10 300U/mg蛋白。该制品在分析型PAGE中呈一条区带。 相似文献
110.
不同来源的肾综合征出血热病毒对Vero细胞的致病变作用 总被引:3,自引:0,他引:3
前文报道,肾综合征出血热病毒76-118株能使Vero细胞产生病变。本文报道76-118株和另11株不同来源的肾综合征出血热病毒(H537、A9、H5、R178、HB55、R22、Z10,沟3、L99、A16和J10)对Vero细胞的致病变作用(CPE )。其中除沟3株外,大部分毒株在感染Vero细胞后的第一代即可见明显的CPE。CPE的特点与76-118株相似,主要是感染细胞粘聚、融合,形成网状结构。CPE能被特异性抗HFRS病毒血清和型特异性单克隆抗体所中和抑制,但不能被特异性抗呼肠孤病毒Ⅲ型免疫血清所中和抑制。HFRS病毒对Vero细胞的致病变作用,对进一步研究HFRS病毒的某些生物学特性及实验方法等均有重要意义。 相似文献