全文获取类型
收费全文 | 1598篇 |
免费 | 175篇 |
国内免费 | 207篇 |
出版年
2024年 | 2篇 |
2023年 | 18篇 |
2022年 | 23篇 |
2021年 | 69篇 |
2020年 | 44篇 |
2019年 | 89篇 |
2018年 | 85篇 |
2017年 | 50篇 |
2016年 | 75篇 |
2015年 | 117篇 |
2014年 | 141篇 |
2013年 | 132篇 |
2012年 | 155篇 |
2011年 | 135篇 |
2010年 | 120篇 |
2009年 | 107篇 |
2008年 | 105篇 |
2007年 | 62篇 |
2006年 | 79篇 |
2005年 | 82篇 |
2004年 | 44篇 |
2003年 | 47篇 |
2002年 | 58篇 |
2001年 | 33篇 |
2000年 | 14篇 |
1999年 | 16篇 |
1998年 | 17篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有1980条查询结果,搜索用时 62 毫秒
41.
Xuan He Dan Li Zhenwu Luo Hua Liang Hong Peng Yangyang Zhao Nidan Wang Donghua Liu Chuan Qin Qiang Wei Huimin Yan Yiming Shao 《PloS one》2013,8(2)
Increasing evidence indicates that antibody-dependent cellular cytotoxicity (ADCC) contributes to the control of HIV/SIV infection. However, little is known about the ADCC function of natural killer (NK) cells in non-human primate model. Here we demonstrated that ADCC function of NK cells was significantly compromised in chronic SIV/SHIV infection, correlating closely with the expression of FcγRIIIa receptor (CD16) on NK cells. CD32, another class of IgG Fc receptors, was identified on NK cells with higher expression in the infected macaques and the blockade of CD32 impacted the ability of NK cells to respond to antibody-coated target cells. The inhibition of matrix metalloproteases (MMPs), a group of enzymes normally involved in tissue/receptor remodeling, could restore NK cell-mediated ADCC with increased CD16 expression on macaque NK cells. These data offer a clearer understanding of NK cell-mediated ADCC in rhesus macaques, which will allow us to evaluate the ADCC repertoire arising from preclinical vaccination studies in non-human primates and inform us in the future design of effective HIV vaccination strategies. 相似文献
42.
43.
【背景】植物根际促生菌(plant growth-promoting rhizobacteria,PGPR)在根际的定殖是其发挥作用的基础,直观有效的跟踪技术和定量方法是研究PGPR在根际原位分布规律的重要工具。【目的】建立一种马铃薯黑痣病病原菌——立枯丝核菌拮抗菌QHZ11的实时荧光定量PCR快速检测体系,并检测拮抗菌QHZ11在马铃薯根际的动态变化。【方法】根据GenBank中登录的类芽孢杆菌及近源菌株gyrB基因序列差异筛选特异性引物,优化反应条件;通过盆栽试验对马铃薯根际拮抗菌进行快速检测。盆栽试验设3个处理,T1:对照(无菌水,CK);T2:QHZ11菌悬液灌土(QHZ11);T3:将功能菌在有机肥中进行二次固体发酵制成生物有机肥(BOF11)。【结果】筛选出拮抗菌QHZ11的专用引物为gyrB-F/gyrB-R;建立的拮抗菌QHZ11实时荧光定量PCR检测方法特异性好、灵敏度高且重复性较好,线性相关系数为0.999 8,检测组内变异系数均在1%以内,扩增效率为0.9,可检测出1×103?1×1010 copies/g-soil的拮抗菌,具有检出限低和扩增效率高的特点。盆栽试验结果发现,T3处理马铃薯根际拮抗菌QHZ11的数量从接种的第10天即高出T2处理一个数量级,并于马铃薯盛花期(接种后第60天)达到峰值,说明二次固体发酵增加了拮抗菌在根际土壤中的存活和繁殖。【结论】建立的实时荧光定量PCR快速检测体系灵敏、高效,可为研究拮抗菌在马铃薯根际原位分布以及与病原菌的互作方面提供便捷有效的方法。 相似文献
44.
45.
Chuan Hong Georgia Salanti Sally C. Morton Richard D. Riley Haitao Chu Stephen E. Kimmel Yong Chen 《Biometrics》2020,76(4):1240-1250
Small study effects occur when smaller studies show different, often larger, treatment effects than large ones, which may threaten the validity of systematic reviews and meta-analyses. The most well-known reasons for small study effects include publication bias, outcome reporting bias, and clinical heterogeneity. Methods to account for small study effects in univariate meta-analysis have been extensively studied. However, detecting small study effects in a multivariate meta-analysis setting remains an untouched research area. One of the complications is that different types of selection processes can be involved in the reporting of multivariate outcomes. For example, some studies may be completely unpublished while others may selectively report multiple outcomes. In this paper, we propose a score test as an overall test of small study effects in multivariate meta-analysis. Two detailed case studies are given to demonstrate the advantage of the proposed test over various naive applications of univariate tests in practice. Through simulation studies, the proposed test is found to retain nominal Type I error rates with considerable power in moderate sample size settings. Finally, we also evaluate the concordance between the proposed tests with the naive application of univariate tests by evaluating 44 systematic reviews with multiple outcomes from the Cochrane Database. 相似文献
46.
Lin Xin Li Liu Chuan Liu Li-Qiang Zhou Qi Zhou Yi-Wu Yuan Shi-Hao Li Hou-Ting Zhang 《Journal of cellular physiology》2020,235(3):2643-2654
Cancer stem cells are undifferentiated cancer cells that have self-renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in regulating gene expression during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence-activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (−) cells. Quantitative real-time polymerase chain reaction (PCR) revealed that the miR-7-5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine-deprived medium. The downregulation of miR-7-5p results from the increased DNA methylation in the promoter region using the methylation-specific PCR. Overexpression of miR-7-5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR-7-5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR-7-5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment. 相似文献
47.
Zhong-Wei Liu Xiao-Lin Niu Kun-Lun Chen Yu-Jie Xing Xuan Wang Chuan Qiu Deng-Feng Gao 《Biological trace element research》2013,153(1-3):220-228
The possible mechanism of adriamycin (ADR) and/or selenium (Se) deficiency-induced cardiac dysfunction, and cardioprotective effects of Se against ADR-induced cardiac toxicity were investigated in this study. Cardiac function was evaluated by plasma brain natriuretic peptide level and echocardiographic and hemodynamic parameters. Cardiac glutathione peroxidase (GPx) activity was assessed spectrophotometrically. Expression of ATP-sensitive potassium channels (KATP) subunits—SUR2A and Kir6.2—were examined by real-time PCR and Western blotting. The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co-administration of ADR and Se deficiency. Mechanically, it is novel for us to find down-regulation of KATP subunits gene expression in cardiac tissue after administration of ADR or Se deficiency, and more significant inhibition of cardiac KATP gene expression was identified after co-administration of ADR and Se deficiency. Furthermore, cardiac toxicity of ADR was found alleviated by Se supplementation, accompanied by restoring of cardiac GPx activity and cardiac KATP gene expression. These results indicate that decreased expression of cardiac KATP is involved in adriamycin and/or Se deficiency-induced cardiac dysfunction; Se deficiency exacerbates adriamycin-induced cardiac dysfunction by future inhibition of KATP expression; Se supplementation seems to protect against adriamycin-induced cardiac dysfunction via restoring KATP expression, showing potential clinical application in cancer chemotherapy. 相似文献
48.
Jo Meagan Garner Meiyun Fan Chuan He Yang Ziyun Du Michelle Sims Andrew M. Davidoff Lawrence M. Pfeffer 《The Journal of biological chemistry》2013,288(36):26167-26176
Malignant gliomas are locally aggressive, highly vascular tumors that have a dismal prognosis, and present therapies provide little improvement in the disease course and outcome. Many types of malignancies, including glioblastoma, originate from a population of cancer stem cells (CSCs) that are able to initiate and maintain tumors. Although CSCs only represent a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance drives tumorigenesis. Therefore, it is imperative to identify pathways associated with CSCs to devise strategies to selectively target them. In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. Glioma CSCs were isolated and maintained in vitro using an adherent culture system, and the biological properties were compared with the traditional cultures of CSCs grown as multicellular spheres under nonadherent culture conditions. Interestingly, both adherent and spheroid glioma CSCs show constitutive activation of the STAT3/NF-κB signaling pathway and up-regulation of STAT3- and NF-κB-dependent genes. Gene expression profiling also identified components of the Notch pathway as being deregulated in glioma CSCs, and the deregulated expression of these genes was sensitive to treatment with STAT3 and NF-κB inhibitors. This finding is particularly important because Notch signaling appears to play a key role in CSCs in a variety of cancers and controls cell fate determination, survival, proliferation, and the maintenance of stem cells. The constitutive activation of STAT3 and NF-κB signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma. 相似文献
49.
Su‐Lan Liao Yen‐Chuan Ou Cheng‐Yi Chang Wen‐Ying Chen Yu‐Hsiang Kuan Wen‐Yi Wang Hung‐Chuan Pan Chun‐Jung Chen 《Journal of neurochemistry》2013,127(2):271-282
Energy failure and oxidative stress have been implicated in the pathogenesis of ischemia. Here, we report a potential link between cytosolic phospholipase A2 (cPLA2) activation and energy failure/oxidative stress‐induced astrocyte damage involving reactive oxygen species (ROS), protein kinase C‐α (PKC‐α), Src, Raf, and extracellular signal‐regulated kinase (ERK) signaling and concurrent elevation of endogenous chelatable zinc. Energy failure and oxidative stress were produced by treating astrocytes with glycolytic inhibitor iodoacetate and glutathione chelator diethylmaleate, respectively. Diethylmaleate and iodoacetate in combination caused augmented damage to astrocytes in a time‐ and concentration‐dependent manner. The cell death caused by diethylmaleate/iodoacetate was accompanied by increased ROS generation, PKC‐α membrane translocation, Src, Raf, ERK, and cPLA2 phosphorylation. Pharmacological studies revealed that these activations all contributed to diethylmaleate/iodoacetate‐induced astrocyte death. Intriguingly, the mobilization of endogenous chelatable zinc was observed in diethylmaleate/iodoacetate‐treated astrocytes. Zinc appears to act as a downstream mediator in response to diethylmaleate/iodoacetate treatment because of the attenuating effects of its chelator N,N,N′,N′‐tetrakis(2‐pyridylmethyl)ethylenediamine. These observations indicate that ROS/PKC‐α, Src/Raf/ERK signaling and cPLA2 are active participants in diethylmaleate/iodoacetate‐induced astrocyte death and contribute to a vicious cycle between the depletion of ATP/glutathione and the mobilization of chelatable zinc as critical upstream effectors in initiating cytotoxic cascades.
50.
Xiang Yu Zhao Ying Hua Su Chuan Li Zhang Liang Wang Xing Guo Li Xian Sheng Zhang 《Plant Cell, Tissue and Organ Culture》2013,112(1):65-74
In vitro organogenesis is well-controlled and thus provides an ideal system to study mechanisms of plant organ development. Although it has been well investigated for a long time that exogenous hormones play important roles in determining the types of organs regenerated in vitro, there is currently limited information available for other key factors that mediate de novo organ regeneration. Here, we reported simple and efficient one-step processes for evaluating capacities of inflorescence stem-derived in vitro organogenesis between two different ecotypes in Arabidopsis. Different types of organs, including shoots and roots were initiated from inflorescence stem explants cultured on the media containing 216 combinations of exogenous auxin and cytokinin. Further, we showed that Wassilewskija ecotype had the much higher shoot regeneration capacity than Columbia with different combinations of hormones, indicating that the ecotype is an essential factor determining de novo organogenesis. Our results also suggested that the defined expression patterns of genes involved in auxin and cytokinin biosynthesis were correlated with the variations in organogenesis capacities between the two ecotypes. Thus, in vitro organogenesis is likely regulated by ecotypes through mediating endogenous hormonal biosynthesis. 相似文献