全文获取类型
收费全文 | 3007篇 |
免费 | 238篇 |
国内免费 | 319篇 |
专业分类
3564篇 |
出版年
2024年 | 8篇 |
2023年 | 59篇 |
2022年 | 130篇 |
2021年 | 172篇 |
2020年 | 127篇 |
2019年 | 131篇 |
2018年 | 168篇 |
2017年 | 100篇 |
2016年 | 139篇 |
2015年 | 198篇 |
2014年 | 230篇 |
2013年 | 224篇 |
2012年 | 271篇 |
2011年 | 261篇 |
2010年 | 166篇 |
2009年 | 131篇 |
2008年 | 166篇 |
2007年 | 161篇 |
2006年 | 128篇 |
2005年 | 86篇 |
2004年 | 88篇 |
2003年 | 52篇 |
2002年 | 73篇 |
2001年 | 45篇 |
2000年 | 31篇 |
1999年 | 41篇 |
1998年 | 33篇 |
1997年 | 30篇 |
1996年 | 17篇 |
1995年 | 15篇 |
1994年 | 13篇 |
1993年 | 12篇 |
1992年 | 17篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1980年 | 1篇 |
排序方式: 共有3564条查询结果,搜索用时 15 毫秒
131.
Qiao Lu Meixing Yu Chongyang Shen Xiaoping Chen Ting Feng Yongchao Yao Jinrong Li Hong Li Wenwei Tu 《PloS one》2014,9(12)
Human induced pluripotent stem cells (hiPSCs) have potential applications in cell replacement therapy and regenerative medicine. However, limited information is available regarding the immunologic features of iPSCs. In this study, expression of MHC and T cell co-stimulatory molecules in hiPSCs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral blood mononuclear cells were examined. We found that no-integrate hiPSCs had no MHC-II and T cell co-stimulatory molecules expressions but had moderate level of MHC-I and HLA-G expressions. In contrast to human skin fibroblasts (HSFs) which significantly induced allogeneic T cell activation and proliferation, hiPSCs failed to induce allogeneic CD45+ lymphocyte and CD8+ T cell activation and proliferation but could induce a low level of allogeneic CD4+ T cell proliferation. Unlike HSFs which induced allogeneic lymphocytes to produce high levels of IFN-γ, TNF-α and IL-17, hiPSCs only induced allogeneic lymphocytes to produce IL-2 and IL-10, and promote IL-10-secreting regulatory T cell (Treg) generation. Our study suggests that the integration-free hiPSCs had low or negligible immunogenicity, which may result from their induction of IL-10-secreting Treg. 相似文献
132.
Fuyuan Li Ning Ma Ruiqi Zhao Guodong Wu Yanfen Zhang Yu Qiao Dong Han Ya Xu Ying Xiang Bingzhu Yan Jianfeng Jin Guixiang Lv Lei Wang Changqing Xu Xu Gao Shanshun Luo 《Journal of cellular and molecular medicine》2014,18(6):966-974
The transition from liver fibrosis to hepatocellular carcinoma (HCC) has been suggested to be a continuous and developmental pathological process. MicroRNAs (miRNAs) are recently discovered molecules that regulate the expression of genes involved in liver disease. Many reports demonstrate that miR‐483‐5p and miR‐483‐3p, which originate from miR‐483, are up‐regulated in HCC, and their oncogenic targets have been identified. However, recent studies have suggested that miR‐483‐5p/3p is partially down‐regulated in HCC samples and is down‐regulated in rat liver fibrosis. Therefore, the aberrant expression and function of miR‐483 in liver fibrosis remains elusive. In this study, we demonstrate that overexpression of miR‐483 in vivo inhibits mouse liver fibrosis induced by CCl4. We demonstrate that miR‐483‐5p/3p acts together to target two pro‐fibrosis factors, platelet‐derived growth factor‐β and tissue inhibitor of metalloproteinase 2, which suppress the activation of hepatic stellate cells (HSC) LX‐2. Our work identifies the pathway that regulates liver fibrosis by inhibiting the activation of HSCs. 相似文献
133.
Jiong-Ming Sui Bao-Tai Guo Jing-Shan Wang Li-Xian Qiao Yong Zhou Hong-Gen Zhang Ming-Hong Gu Guo-Hua Liang 《Plant Molecular Biology Reporter》2012,30(1):187-194
A semidwarf line of Indica rice, Xinguiai, was derived from the progeny of a cross between the double dwarf mutant Xinguiaishuangai and the wild-type
variety Nanjing 6. The semidwarf phenotype was controlled by the semidwarf gene, sdg. The second sheath and shoot elongation responses of the dwarf mutant to exogenous gibberellin (GA3) showed that sdg was insensitive to gibberellin (GA), and its endogenous GAs content was higher than that in wild-type cultivars. The SDG gene was cloned by a map-based cloning method and sequencing analysis revealed that the coding region of sdg had a single nucleotide substitution resulting in a single amino acid change from alanine to threonine. A cleaved amplified
polymorphic sequence marker was designed according to sequences from mutant and wild-type materials. This sequence marker
could be used to distinguish wild types and mutants, and thus, could be used for molecular marker-assisted selection. The
dwarf phenotype of the sdg mutant was restored to a normal phenotype by introducing the wild-type SDG gene. Rice transformation experiments and GUS staining demonstrated that the SDG gene was predominantly expressed in vegetative organs. 相似文献
134.
Duo Wu Ke Qiao Meng Feng Yongfeng Fu Junlong Cai Yihong Deng Hiroshi Tachibana Xunjia Cheng 《The Journal of eukaryotic microbiology》2018,65(2):191-199
Acanthamoeba spp. can be parasitic in certain situations and are responsible for serious human infections, including Acanthamoeba keratitis, granulomatous amoebic encephalitis, and cutaneous acanthamoebiasis. We analyzed the fatty acid composition of Acanthamoeba castellanii trophozoites and tested the inhibitory activity of the main fatty acids, oleic acid and arachidonic acid, in vitro. Oleic acid markedly inhibited the growth of A. castellanii, with trophozoite viability of 57.4% at a concentration of 200 μM. Caspase‐3 staining and annexin V assays showed that apoptotic death occurred in A. castellanii trophozoites. Quantitative PCR and dot blot analysis showed increased levels of metacaspase and interleukin‐1β converting enzyme, which is also an indication of apoptosis. In contrast, arachidonic acid showed negligible inhibition of growth of A. castellanii trophozoites. Stimulated expression of Atg3, Atg8 and LC3A/B genes and monodansylcadaverine labeling suggested that oleic acid induces apoptosis by triggering autophagy of trophozoites. 相似文献
135.
Recently, the use of hybrid double network (DN) hydrogels has become prominent due to their enhanced mechanical properties, which has opened the door for new applications of these soft materials. Only a few of these gels have demonstrated both injectable and moldable capabilities. In this work, we report the mechanical properties, gauge factor (GF) values and demonstrate both the injectability and moldability of a gelatin/polyacrylamide DN hydrogel. We optimized several parameters, such as, gelatin to polyacrylamide ratio, reactant concentrations and metal ion concentration, to produce a gelatin/polyacrylamide hydrogel with superior mechanical properties. The highest water content gel was capable of withstanding strains of 5000% before failure. These gels were facilely injected into molds where they effectively changed shape and maintained similar properties prior to remolding. When 20 mM calcium was doped into a similar gel, a tensile strength of 1.71 MPa was achieved. Aside from improving the mechanical properties of the gels, both Ca2+ and Mg2+ also improved their conductivity, so they were tested for use as strain sensors. The sensitivity of the hydrogel strain sensors were measured using the GF. For the 20 mM Ca2+ hydrogel, these GF values ranged from 1.63 to 6.85 for strains of 100% to 2100% respectively. Additionally, the sensors showed good stability over continuous cyclic stretching, demonstrating their long term reliability for strain sensing. 相似文献
136.
Li Jiang Yanguo Qiao Zhenghui Wang Xiuzhu Ma Haichao Wang Jian Li 《Journal of cellular physiology》2020,235(1):380-393
Atherosclerosis (AS), a chronic disorder of large arteries, is the underlying pathological process of heart disease and stroke. Former researchers have found that microRNAs (miRs) are involved in the several key processes of AS. Apolipoprotein E knockout (ApoE−/−) mice fed a high-fat-diet (HFD) to establish AS model. The expression of miR-103 was characterized in the mice model. The effects of miR-103 on inflammation and endoplasmic reticulum stress (ERS) were analyzed when the expression of miR-103 was inhibited in ApoE −/− mice fed an HFD and human aortic endothelial cells (HAECs) exposed to oxidized low-density lipoprotein (ox-LDL). The relationship between miR-103 and phosphatase and tensin homolog (PTEN) was identified by luciferase activity detection and real-time quantitative polymerase chain reaction (RT-qPCR). Gain- and loss-function approaches were further applied for investigating the regulatory effects of miR-103 and PTEN on ERS. Role of MAPK signaling was then analyzed using PD98059 to block this pathway. miR-103 was highly expressed in the ApoEApoE −/− mice fed an HFD. Downregulation of miR-103 suppressed inflammation and ERS in endothelial cells isolated from ApoE −/− mice fed a HFD and ox-LDL-exposed HAECs. In addition, miR-103 can target PTEN and downregulate its expression. Overexpression of PTEN reversed the miR-103-induced activation of MAPK signaling. Moreover, PTEN upregulation or MAPK signaling inhibition ease miR-103-induced inflammation and ERS in vivo and in vitro. Thus, miR-103 depletion restrains the progression of AS through blocking PTEN-mediated MAPK signaling. 相似文献
137.
Feng Li Biyun Chen Kun Xu Jinfeng Wu Weilin Song Ian Bancroft Andrea L. Harper Martin Trick Shengyi Liu Guizhen Gao Nian Wang Guixin Yan Jiangwei Qiao Jun Li Hao Li Xin Xiao Tianyao Zhang Xiaoming Wu 《DNA research》2014,21(4):355-367
Association mapping can quickly and efficiently dissect complex agronomic traits. Rapeseed is one of the most economically important polyploid oil crops, although its genome sequence is not yet published. In this study, a recently developed 60K Brassica Infinium® SNP array was used to analyse an association panel with 472 accessions. The single-nucleotide polymorphisms (SNPs) of the array were in silico mapped using ‘pseudomolecules’ representative of the genome of rapeseed to establish their hypothetical order and to perform association mapping of seed weight and seed quality. As a result, two significant associations on A8 and C3 of Brassica napus were detected for erucic acid content, and the peak SNPs were found to be only 233 and 128 kb away from the key genes BnaA.FAE1 and BnaC.FAE1. BnaA.FAE1 was also identified to be significantly associated with the oil content. Orthologues of Arabidopsis thaliana HAG1 were identified close to four clusters of SNPs associated with glucosinolate content on A9, C2, C7 and C9. For seed weight, we detected two association signals on A7 and A9, which were consistent with previous studies of quantitative trait loci mapping. The results indicate that our association mapping approach is suitable for fine mapping of the complex traits in rapeseed. 相似文献
138.
Yan-Ning Qiao Wei-Qi He Cai-Ping Chen Cheng-Hai Zhang Wei Zhao Pei Wang Lin Zhang Yan-Ze Wu Xiao Yang Ya-Jing Peng Ji-Min Gao Kristine E. Kamm James T. Stull Min-Sheng Zhu 《The Journal of biological chemistry》2014,289(32):22512-22523
Myosin light chain phosphatase with its regulatory subunit, myosin phosphatase target subunit 1 (MYPT1) modulates Ca2+-dependent phosphorylation of myosin light chain by myosin light chain kinase, which is essential for smooth muscle contraction. The role of MYPT1 in vascular smooth muscle was investigated in adult MYPT1 smooth muscle specific knock-out mice. MYPT1 deletion enhanced phosphorylation of myosin regulatory light chain and contractile force in isolated mesenteric arteries treated with KCl and various vascular agonists. The contractile responses of arteries from knock-out mice to norepinephrine were inhibited by Rho-associated kinase (ROCK) and protein kinase C inhibitors and were associated with inhibition of phosphorylation of the myosin light chain phosphatase inhibitor CPI-17. Additionally, stimulation of the NO/cGMP/protein kinase G (PKG) signaling pathway still resulted in relaxation of MYPT1-deficient mesenteric arteries, indicating phosphorylation of MYPT1 by PKG is not a major contributor to the relaxation response. Thus, MYPT1 enhances myosin light chain phosphatase activity sufficient for blood pressure maintenance. Rho-associated kinase phosphorylation of CPI-17 plays a significant role in enhancing vascular contractile responses, whereas phosphorylation of MYPT1 in the NO/cGMP/PKG signaling module is not necessary for relaxation. 相似文献
139.
140.