全文获取类型
收费全文 | 9610篇 |
免费 | 906篇 |
国内免费 | 537篇 |
出版年
2024年 | 1篇 |
2023年 | 105篇 |
2022年 | 154篇 |
2021年 | 383篇 |
2020年 | 348篇 |
2019年 | 395篇 |
2018年 | 381篇 |
2017年 | 295篇 |
2016年 | 441篇 |
2015年 | 602篇 |
2014年 | 751篇 |
2013年 | 794篇 |
2012年 | 921篇 |
2011年 | 902篇 |
2010年 | 526篇 |
2009年 | 478篇 |
2008年 | 525篇 |
2007年 | 507篇 |
2006年 | 424篇 |
2005年 | 336篇 |
2004年 | 251篇 |
2003年 | 287篇 |
2002年 | 201篇 |
2001年 | 164篇 |
2000年 | 143篇 |
1999年 | 147篇 |
1998年 | 89篇 |
1997年 | 66篇 |
1996年 | 81篇 |
1995年 | 65篇 |
1994年 | 44篇 |
1993年 | 29篇 |
1992年 | 51篇 |
1991年 | 37篇 |
1990年 | 25篇 |
1989年 | 30篇 |
1988年 | 12篇 |
1987年 | 17篇 |
1986年 | 13篇 |
1985年 | 13篇 |
1984年 | 7篇 |
1983年 | 10篇 |
1982年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Wei-Qing Li Hong-Yu Yu Yi-Ming Li Xiang Wang Jin He Hong-Zhu Yan Dao-Hua Yang Xiao-Jun Wu Li-Jun Hou Hui-Min Liu Chun-Yan Xia Yi-Cheng Lu 《Biochemical and biophysical research communications》2014
Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n = 60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment. 相似文献
2.
3.
【目的】猪链球菌1、2、14和1/2型间存在单向或双向的交叉抗原性,这种交叉抗原性的产生原因至今未被揭示。【方法】采用Sephacryl S-300凝胶层析柱对猪链球菌14和1/2型荚膜多糖进行分离纯化,经苯酚-硫酸检测和dot-ELISA辅助鉴定,确定荚膜多糖成分。采用高效凝胶渗透色谱法测定14和1/2型猪链球菌荚膜多糖分子量分别为487.38 kDa和512.72 kDa。【结果】经柱前衍生高效液相色谱法、荧光标记液相色谱法和核磁共振测定14和1/2型猪链球菌荚膜多糖单糖组成分别为:Glc/Gal/GlcNAc/Rha/Neu5Ac(1∶2.94∶1.35∶0.24∶0.37)和Glc/Gal/GlcNAc/GalNAc/Rha/Neu5Ac(1∶1.67∶1.05∶0.93∶0.72∶0.7)。并与已知的猪链球菌1、2型荚膜多糖的单糖组成进行比较分析,发现4种血清型荚膜多糖都具有Glc、GlcNAc、Gal和Neu5Ac,但单糖组成和比列并无明显相似性,这种交叉抗原性可能是由于荚膜多糖的空间结构相似性和(或)细胞表面的其他成分引起的。 相似文献
4.
Diverse monosaccharide analysis methods have been established for a long time, but few methods are available for a complete monosaccharide analysis of glycosaminoglycans (GAGs) and certain acidolysis-resistant components derived from GAGs. In this report, a reversed-phase high-performance liquid chromatography (RP–HPLC) method with pre-column 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization was established for a complete monosaccharide analysis of GAGs. Good separation of glucosamine/mannosamine (GlcN/ManN) and glucuronic acid/iduronic acid (GlcA/IdoA) was achieved. This method can also be applied to analyze the acidolysis-resistant disaccharides derived from GAGs, and the sequences of these disaccharides were confirmed by electrospray ionization–collision-induced dissociation–tandem mass spectrometry (ESI–CID–MS/MS). These unique disaccharides could be used as markers to distinguish heparin/heparan sulfate (HP/HS), chondroitin sulfate/dermatan sulfate (CS/DS), and hyaluronic acid (HA). 相似文献
5.
Li Huang Qinfang Liu Lijie Zhang Quan Zhang Liang Hu Changyao Li Shengnan Wang Jiangnan Li Yuanfeng Zhang Huibin Yu Yan Wang Zhaohua Zhong Tao Xiong Xueshan Xia Xiaojun Wang Li Yu Guohua Deng Xuehui Cai Shangjin Cui Changjiang Weng 《The Journal of biological chemistry》2015,290(46):27618-27632
TRAF family member-associated NF-κB activator (TANK) is a negative regulator of canonical NF-κB signaling in the Toll-like receptor- and B-cell receptor-mediated signaling pathways. However, functions of TANK in viral infection-mediated NF-κB activation remain unclear. Here, we reported that TANK was cleaved by encephalomyocarditis virus 3C at the 197 and 291 glutamine residues, which depends on its cysteine protease activity. In addition, encephalomyocarditis virus 3C impaired the ability of TANK to inhibit TRAF6-mediated NF-κB signaling. Interestingly, we found that several viral proteases encoded by the foot and mouth disease virus, porcine reproductive and respiratory syndrome virus, and equine arteritis virus also cleaved TANK. Our results suggest that TANK is a novel target of some viral proteases, indicating that some positive RNA viruses have evolved to utilize their major proteases to regulate NF-κB activation. 相似文献
6.
7.
8.
Yue Qiu Zuo-Yang Zhang Wei-Dong Du Lei Ye Song Xu Xian-Bo Zuo Fu-Sheng Zhou Gang Chen Xue-Ling Ma Marion E. Schneider Hong-Zhen Xia Yuan Zhou Ji-Feng Wu Xu Yuan-Hong Xue-Jun Zhang 《Gene》2014
The purpose of this study was to investigate whether risk of gastric cancer (GC) was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We detected twenty-six SNPs in this gene cluster containing steroidogenic acute regulatory-related lipid transfer domain containing 3 (STARD3), protein phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1-like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2 (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls by Sequenom. We found no associations between genetic variations and GC risk. However, haplotype analysis implied that the haplotype CCCT of STARD3 (rs9972882, rs881844, rs11869286 and rs1877031) conferred a protective effect on the susceptibility to GC (P = 0.043, odds ratio [OR] = 0.805, 95% confidence intervals [95% CI] = 0.643–0.992). The STARD3 rs1877031 TC genotype endued histogenesis of gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P = 0.021, OR = 2.882, 95% CI = 1.173–7.084). We examined the expression of STARD3 in 243 tumor tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using immumohistochemical (IHC) analysis and tissue microarrays (TMA). The expression of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues and significantly correlated with gender (P = 0.004), alcohol drinking (P < 0.001), tumor location (P = 0.007), histological type (P = 0.005) and differentiation (P = 0.023) in GC. We concluded that the combined effect of haplotype CCCT of STARD3 might affect GC susceptibility. STARD3 expression might be related to the tumorigenesis of GC in the Chinese population. 相似文献
9.
10.
Research has shown that microRNAs are promising biomarkers that can be used to promote a more accurate diagnosis of cancer. In this study, we developed an integrated multi-step selection process to analyze available high-throughput datasets to obtain information on microRNAs as cancer biomarkers. Applying this approach to the microRNA expression profiles of prostate cancer and the datasets in The Cancer Genome Atlas Data Portal, we identified miRNA-182, miRNA-200c and miRNA-221 as possible biomarkers for prostate cancer. The associations between the expressions of these three microRNAs with clinical parameters as well as their diagnostic capability were studied. Several online databases were used to predict the target genes of these three microRNAs, and the results were confirmed by significant statistical correlations. Comparing with the other 18 types of cancers listed in The Cancer Genome Atlas Data Portal, we found that the combination of both miRNA-182 and miRNA-200c being up-regulated and miRNA-221 being down-regulated only happens in prostate cancer. This provides a unique biological characteristic for prostate cancer that can potentially be used for diagnosis based on tissue testing. In addition, our study also revealed that these three microRNAs are associated with the pathological status of prostate cancer. 相似文献