全文获取类型
收费全文 | 5373篇 |
免费 | 403篇 |
国内免费 | 220篇 |
专业分类
5996篇 |
出版年
2024年 | 18篇 |
2023年 | 87篇 |
2022年 | 118篇 |
2021年 | 179篇 |
2020年 | 196篇 |
2019年 | 311篇 |
2018年 | 255篇 |
2017年 | 159篇 |
2016年 | 143篇 |
2015年 | 161篇 |
2014年 | 351篇 |
2013年 | 406篇 |
2012年 | 230篇 |
2011年 | 332篇 |
2010年 | 218篇 |
2009年 | 199篇 |
2008年 | 214篇 |
2007年 | 252篇 |
2006年 | 197篇 |
2005年 | 164篇 |
2004年 | 142篇 |
2003年 | 119篇 |
2002年 | 111篇 |
2001年 | 87篇 |
2000年 | 77篇 |
1999年 | 98篇 |
1998年 | 73篇 |
1997年 | 82篇 |
1996年 | 84篇 |
1995年 | 53篇 |
1994年 | 43篇 |
1993年 | 45篇 |
1992年 | 51篇 |
1991年 | 56篇 |
1990年 | 47篇 |
1989年 | 51篇 |
1988年 | 48篇 |
1987年 | 47篇 |
1986年 | 53篇 |
1985年 | 59篇 |
1984年 | 69篇 |
1983年 | 50篇 |
1982年 | 64篇 |
1981年 | 38篇 |
1980年 | 46篇 |
1979年 | 35篇 |
1978年 | 16篇 |
1977年 | 12篇 |
1976年 | 15篇 |
1972年 | 10篇 |
排序方式: 共有5996条查询结果,搜索用时 0 毫秒
51.
52.
Nakata H 《Biochemical and biophysical research communications》2007,355(3):842-848
Suramin is a well-known antitrypanosomal drug and a novel experimental agent for the treatment of several cancers. Previous study showed that suramin is an activator of extracellular signal-regulated kinase (ERK1/2) signaling in several cell lines including Chinese hamster ovary cells, although the physiological relevance of this activation remains uncertain. Here, it was shown that suramin enhances neurite outgrowth concomitant with activation of ERK1/2 in Neuro-2a cells, a neuronal cell line. These neurite outgrowth and ERK1/2 activation were significantly inhibited by PD98059, an inhibitor of mitogen-activated protein kinase kinase, as well as by activation of endogenous adenosine A2A receptors. The suramin-induced phosphorylation of ERK1/2 was also inhibited by inhibitors of Src family kinases. This attenuation of ERK1/2 activity was accompanied by a significant decrease in suramin-induced neurite outgrowth. These results suggest that suramin activates the Src/ERK1/2 signaling pathway that induces neurite outgrowth, both of which are negatively regulated by cAMP produced in response to activation of endogenous adenosine A2A receptors. 相似文献
53.
Mark D. Gonzalez Carol A. Lichtensteiger Eric R. Vimr 《FEMS microbiology letters》2001,198(2):125-128
With the exception of the polysialic acid capsule (K1 antigen), little is known about other virulence factors needed for systemic infection by Escherichia coli K1, the leading cause of Gram-negative neonatal meningitis in humans. In this work, the functional genomics method of signature-tagged mutagenesis (STM) was adapted to E. coli K1 and the infant-rat model to identify non-capsule virulence genes. Validation of the method was demonstrated by the failure to recover a reconstructed acapsular mutant from bacterial pools used to systemically infect 5-day-old rats. Three new genes required for systemic disease were identified from a total of 192 mutants screened by STM (1.56% hit rate). Gut colonization, Southern blot hybridization, mixed-challenge infection, and DNA sequence analyses showed that the attenuating defects in the mutants were associated with transposon insertions in rfaL (O antigen ligase), dsbA (thiol:disulfide oxidoreductase), and a new gene, puvA (previously unidentified virulence gene A), with no known homologues. The results indicate the ability of STM to identify novel systemic virulence factors in E. coli K1. 相似文献
54.
An experiment was conducted to determine the effect of water stress on nutritional changes in tolerant (DS-4 and Chakwal-86)
and susceptible (DS-17 and Pavon) genotypes in lysimeters. The stress was imposed at different growth stages (pre-anthesis,
post-anthesis, terminal drought). The biomass (dry weight) and Ca, Mg and P concentration decreased with water stress in all
the wheat genotypes. However, the tolerant genotypes had less reduction than susceptible at all the treatments. Potassium
increased in all wheat genotypes due to water stress and was higher in tolerant than susceptible genotypes. Sodium content
was not affected by water stress. 相似文献
55.
通过盆栽试验,采用原子吸收分光光度法和非损伤微测技术,研究了NaHCO3胁迫(300 mmol·L-1)对大洋洲滨藜、四翅滨藜和宁夏枸杞3种灌木离子吸收及运转的影响.结果表明: 随着NaHCO3浓度升高,两种滨藜和宁夏枸杞叶片中Na+含量升高,300 mmol·L-1NaHCO3胁迫下,宁夏枸杞叶肉细胞Na+的外排增加,两种滨藜净Na+外排降低;随着胁迫时间的延长,大洋洲滨藜和宁夏枸杞叶片的K+含量下降,Na+/K+升高,四翅滨藜叶片K+含量升高,Na+/K+降低;随着浓度的升高,宁夏枸杞叶片积累Ca2+减少,Na+/Ca2+高于对照,叶肉细胞Ca2+外排;两种滨藜叶Ca2+含量总体呈升高趋势,叶肉细胞Ca2+表现为内流.在NaHCO3胁迫下,3种灌木通过不同的策略来消除Na+毒害.宁夏枸杞叶片Na+的积累抑制了对Ca2+的吸收;两种滨藜Ca2+的内流促使细胞质中游离Ca2+增加,增加的细胞质\[Ca2+\]cyt防治质膜H+ ATPase去极化,限制K+的外排,从而维持细胞内Na+/K+的平衡,其中四翅滨藜调控Na+/K+平衡的能力较强. 相似文献
56.
Hironori Nishitsuji Ryuichi Sugiyama Makoto Abe Hiroshi Takaku 《The Journal of biological chemistry》2016,291(9):4754-4762
Here, we identify ATP1B3 and fibrillin-1 as novel BST-2-binding proteins. ATP1B3 depletion in HeLa cells (BST-2-positive cells), but not 293T cells (BST-2-negative cells), induced the restriction of HIV-1 production in a BST-2-dependent manner. In contrast, fibrillin-1 knockdown reduced HIV-1 production in 293T and HeLa cells in a BST-2-independent manner. Moreover, NF-κB activation was enhanced by siATP1B3 treatment in HIV-1- and HIV-1ΔVpu-infected HeLa cells. In addition, ATP1B3 silencing induced high level BST-2 expression on the surface of HeLa cells. These results indicate that ATP1B3 is a co-factor that accelerates BST-2 degradation and reduces BST-2-mediated restriction of HIV-1 production and NF-κB activation. 相似文献
57.
Takano Y Yamauchi K Hayakawa K Hiramatsu N Kasai A Okamura M Yokouchi M Shitamura A Yao J Kitamura M 《FEBS letters》2007,581(3):421-426
Expression of nephrin, a crucial component of the glomerular slit diaphragm, is downregulated in patients with proteinuric glomerular diseases. Using conditionally immortalized reporter podocytes, we found that bystander macrophages as well as macrophage-derived cytokines IL-1beta and TNF-alpha markedly suppressed activity of the nephrin gene promoter in podocytes. The cytokine-initiated repression was reversible, observed on both basal and inducible expression, independent of Wilms' tumor suppressor WT1, and caused in part via activation of the phosphatidylinositol-3-kinase/Akt pathway. These results indicated a novel mechanism by which activated macrophages participate in the induction of proteinuria in glomerular diseases. 相似文献
58.
Keenan M. L. Mack Lu Zhai Arrix L. Ryce Wei‐Ming Ni Donald L. DeAngelis J. David Van Dyken 《Ecology letters》2017,20(9):1118-1128
A large body of theory predicts that populations diffusing in heterogeneous environments reach higher total size than if non‐diffusing, and, paradoxically, higher size than in a corresponding homogeneous environment. However, this theory and its assumptions have not been rigorously tested. Here, we extended previous theory to include exploitable resources, proving qualitatively novel results, which we tested experimentally using spatially diffusing laboratory populations of yeast. Consistent with previous theory, we predicted and experimentally observed that spatial diffusion increased total equilibrium population abundance in heterogeneous environments, with the effect size depending on the relationship between r and K. Refuting previous theory, however, we discovered that homogeneously distributed resources support higher total carrying capacity than heterogeneously distributed resources, even with species diffusion. Our results provide rigorous experimental tests of new and old theory, demonstrating how the traditional notion of carrying capacity is ambiguous for populations diffusing in spatially heterogeneous environments. 相似文献
59.
BingZhi Yu Zhe Zhang Xin Deng XiaoYan Xu Chen Feng YanXiao Li Cheng Cui WenHui Su HongMei Zhao DaHai Yu 《中国科学:生命科学英文版》2008,51(9):767-773
Recent studies have suggested that growth factors and hormones play important roles in cell prolif-eration and differentiation during early embryonic development. In the present study, we examined the expression and localization of insulin in the mouse oocytes and one-cell stage embryos by quantitative ELISA, RT-PCR, Western blot and immunofluorescence. In the mouse oocytes and one-cell stage em-bryos, expression of insulin was uniformly distributed in the cytoplasm. We also examined the expres-sion, activity and localization of mTOR (mammalian target of rapamycin) and p70S6K. The expression of mTOR and p70S6K was not significantly different at the cell cycle of mouse one-cell stage embryos. mTOR and S6K were distributed evenly in the cytoplasm at G1, G2 and M phase phase, but at S phase, the distribution of mTOR and S6K was around the pronucleus. At different phases, the activity of mTOR fluctuated. We also used the PI3K specific inhibitor-Wortmannin to investigate the cleavage rate of eggs. The result showed that the rate obviously decreased. When the mTOR specific inhibitor Rapa-mycin was used, the first mitotic division of the mouse one-cell stage embryo was delayed. These re-sults suggested that insulin was expressed both in mouse oocytes and one-cell stage embryos, and may play functional roles in regulation of mouse early embryogenesis by activating the signal pathway of PI3K/PKB/mTOR/S6K. 相似文献
60.