全文获取类型
收费全文 | 40200篇 |
免费 | 3118篇 |
国内免费 | 3070篇 |
专业分类
46388篇 |
出版年
2024年 | 83篇 |
2023年 | 582篇 |
2022年 | 1352篇 |
2021年 | 2246篇 |
2020年 | 1512篇 |
2019年 | 1947篇 |
2018年 | 1790篇 |
2017年 | 1253篇 |
2016年 | 1796篇 |
2015年 | 2574篇 |
2014年 | 3017篇 |
2013年 | 3277篇 |
2012年 | 3600篇 |
2011年 | 3234篇 |
2010年 | 1967篇 |
2009年 | 1756篇 |
2008年 | 2099篇 |
2007年 | 1850篇 |
2006年 | 1543篇 |
2005年 | 1224篇 |
2004年 | 1007篇 |
2003年 | 956篇 |
2002年 | 722篇 |
2001年 | 653篇 |
2000年 | 608篇 |
1999年 | 590篇 |
1998年 | 351篇 |
1997年 | 333篇 |
1996年 | 325篇 |
1995年 | 300篇 |
1994年 | 310篇 |
1993年 | 195篇 |
1992年 | 249篇 |
1991年 | 242篇 |
1990年 | 167篇 |
1989年 | 146篇 |
1988年 | 112篇 |
1987年 | 93篇 |
1986年 | 73篇 |
1985年 | 69篇 |
1984年 | 40篇 |
1983年 | 42篇 |
1982年 | 26篇 |
1981年 | 23篇 |
1980年 | 10篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1973年 | 4篇 |
1969年 | 3篇 |
1968年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
161.
Zhao Zhang Zeyan Li Zhao Liu Xiang Zhang Nengwang Yu Zhonghua Xu 《Journal of cellular biochemistry》2020,121(7):3606-3615
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor. Previous studies have shown that the interaction between tumor cells and microenvironment has an important impact on prognosis. Immune and stromal cells are two vital components of the tumor microenvironment. Our study aimed to better understand and explore the genes involved in immune/stromal cells on prognosis. We used the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm to calculate immune/stromal scores. According to the scores, we divided ccRCC patients from The Cancer Genome Atlas database into low and high groups and identified the genes which were differentially expressed and significantly associated with prognosis. The result of functional enrichment analysis and protein-protein interaction networks indicated that these genes mainly were involved in extracellular matrix and regulation of cellular activities. Then another independent cohort from the International Cancer Genome Consortium database was used to validate these genes. Finally, we acquired a list of microenvironment-related genes that can predict prognosis for ccRCC patients. 相似文献
162.
163.
Fuxin Zhao Jinyu Wu Anquan Xue Yanfeng Su Xiaojing Wang Xianmin Lu Zhonglou Zhou Jia Qu Xiangtian Zhou 《Human genetics》2013,132(8):913-921
Myopia is a refractive error of the eye that is prevalent worldwide. The most extreme form, high myopia, is usually associated with other ocular disorders such as retinal detachment, macular degeneration, cataract, and glaucoma, and is one of leading causes of blindness. The etiology is complex and has not been fully elucidated. In this study, we identified a novel missense variant of the CCDC111 gene (NM_152683.2: c.265T > G; p.Y89D) in a high myopia family by exome sequencing. The variant was identified in 4 patients from an additional 270 sporadic high myopia patients, but not found in 270 controls. The amino acid is highly conserved across species, and variants giving rise to amino acid substitutions are predicted to be functionally damaging. The CCDC111 gene was ubiquitously expressed in primary cell cultures from human eye tissue, including corneal epithelial cells, choroidal melanoma cells, scleral fibroblasts, retinal epithelial cells, retinal Müller cells, and lens capsule epithelial cells. In summary, our results suggested that the CCDC111 may be a susceptibility gene for high myopia. 相似文献
164.
165.
Jian-Hua Li Shen-Ting Zhao Cui-Ying Wu Xiong Cao Miao-Ru Peng Shu-Ji Li Xiao-Ai Liu Tian-Ming Gao 《Neurochemical research》2013,38(10):2216-2226
The destruction of calcium homeostasis is an important factor leading to neurological diseases. Store-operated Ca2+ (SOC) channels are essential for Ca2+ homeostasis in many cell types. However, whether SOC channels are involved in astrocyte activation induced by lipopolysaccharide (LPS) still remains unknown. In this study, we used LPS as an exogenous stimulation to investigate the role of SOC channels in astrocyte activation. Using calcium imaging technology, we first found that SOC channels blockers, 1-[h-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365) and 2-aminoethyldiphenyl borate (2-APB), inhibited LPS induced [Ca2+]i increase, which prompted us to speculate that SOC channels may be involved in LPS induced astrocyte activation. Further experiments confirmed our speculation shown as SOC channels blockers inhibited LPS induced astrocyte activation characterized as cell proliferation by MTS and BrdU assay, raise in glial fibrillary acidic protein expression by immunofluorescence and Western Blot and secretion of interleukin 6 (IL-6) and interleukin 1β (IL-1β) by ELISA. So, our studies showed that SOC channels are involved in LPS-induced astrocyte activation. 相似文献
166.
167.
Zhaojing Zheng Juan Geng Ru-en Yao Caihua Li Daming Ying Yongnian Shen Lei Ying Yongguo Yu Qihua Fu 《Gene》2013
Fanconi anemia is a rare genetic disease characterized by bone marrow failure, multiple congenital malformations, and an increased susceptibility to malignancy. At least 15 genes have been identified that are involved in the pathogenesis of Fanconi anemia. However, it is still a challenge to assign the complementation group and to characterize the molecular defects in patients with Fanconi anemia. In the current study, whole exome sequencing was used to identify the affected gene(s) in a boy with Fanconi anemia. A recurring, non-synonymous mutation was found (c.3971C>T, p.P1324L) as well as a novel frameshift mutation (c.989_995del, p.H330LfsX2) in FANCA gene. Our results indicate that whole exome sequencing may be useful in clinical settings for rapid identification of disease-causing mutations in rare genetic disorders such as Fanconi anemia. 相似文献
168.
169.
Yinghui Li Yuxiao Huang Jiao Liang Zhikai Xu Yan Shen Ning Zhang Zhongxiang Liu Ya Zhao 《Molecular biology reports》2013,40(4):2781-2787
CD8+ T cells play an important role in early HIV infection. However, HIV has the capacity to avoid specific CTL responses due to a high rate of mutation under selection pressure. Although the HIV proteins, gag and pol, are relatively conserved, these sequences generate low-affinity MHC-associated epitopes that are poorly immunogenic. Here, we applied an approach that enhanced the immunogenicity of low-affinity HLA-A2.1-binding peptides. The first position with tyrosine (P1Y) substitution enhanced the affinity of HLA-A2.1-associated peptides without altering their antigenic specificity. More importantly, P1Y variants efficiently stimulated in vivo native peptide-specific CTL that also recognized the corresponding naturally processed epitope. The potential to generate CTL against any low-affinity HLA-A2.1-associated peptide provides us with the necessary technique for identification of virus cryptic epitopes for development of peptide-based immunotherapy. Therefore, identification and modification of the cryptic epitopes of gal and pol provides promising candidates for HIV immunotherapy dependent upon efficient presentation by virus cells. Furthermore, this may be a breakthrough that overcomes the obstacle of immune escape caused by high rates of mutation. In this study, bioinformatics analysis was used to predict six low-affinity cryptic HIV gag and pol epitopes presented by HLA-A*0201. A HIV compound multi-CTL epitope gene was constructed comprising the gene encoding the modified cryptic epitope and the HIV p24 antigen, which induced a strong CD8+ T cell immune response regardless of the mutation. This approach represents a novel strategy for the development of safe and effective HIV prophylactic and therapeutic vaccines. 相似文献
170.
Yuyun Huang Huilong ChenJianmiao Wang Hansvin BunjhooWeining Xiong Yongjian XuJianping Zhao 《Gene》2013