全文获取类型
收费全文 | 3370篇 |
免费 | 346篇 |
国内免费 | 355篇 |
出版年
2024年 | 3篇 |
2023年 | 42篇 |
2022年 | 60篇 |
2021年 | 206篇 |
2020年 | 131篇 |
2019年 | 161篇 |
2018年 | 156篇 |
2017年 | 105篇 |
2016年 | 142篇 |
2015年 | 187篇 |
2014年 | 261篇 |
2013年 | 246篇 |
2012年 | 316篇 |
2011年 | 285篇 |
2010年 | 194篇 |
2009年 | 168篇 |
2008年 | 176篇 |
2007年 | 155篇 |
2006年 | 141篇 |
2005年 | 135篇 |
2004年 | 137篇 |
2003年 | 115篇 |
2002年 | 101篇 |
2001年 | 91篇 |
2000年 | 71篇 |
1999年 | 73篇 |
1998年 | 41篇 |
1997年 | 26篇 |
1996年 | 24篇 |
1995年 | 27篇 |
1994年 | 19篇 |
1993年 | 18篇 |
1992年 | 6篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1965年 | 1篇 |
1955年 | 1篇 |
1951年 | 2篇 |
排序方式: 共有4071条查询结果,搜索用时 14 毫秒
61.
Pei Xiao Hongxia Yang Dongdong Di Dongri Piao Qiuxiang Zhang Ruie Hao Suxia Yao Rong Zhao Fanfei Zhang Guozhong Tian Hongyan Zhao Weixing Fan Buyun Cui Hai Jiang 《PloS one》2015,10(1)
Background
Brucellosis presents a significant economic burden for China because it causes reproductive failure in host species and chronic health problems in humans. These problems can involve multiple organs. Brucellosis is highly endemic in Shanxi Province China. Molecular typing would be very useful to epidemiological surveillance. The purpose of this study was to assess the diversity of Brucella melitensis strains for epidemiological surveillance. Historical monitoring data suggest that Brucella melitensis biovar 3 is the predominant strain associated with the epidemic of brucellosis in Shanxi Province.Methods/Principal Findings
Multiple-locus variable-number repeat analysis (MLVA-16) and hypervariable octameric oligonucleotide fingerprinting (HOOF-print) were used to type a human-hosted Brucella melitensis population (81 strains). Sixty-two MLVA genotypes (discriminatory index: 0.99) were detected, and they had a genetic similarity coefficient ranging from 84.9% to 100%. Eighty strains of the population belonged to the eastern Mediterranean group with panel 1 genotypes 42 (79 strains) and 43 (1 strain). A new panel 1 genotype was found in this study. It was named 114 MLVAorsay genotype and it showed similarity to the two isolates from Guangdong in a previous study. Brucella melitensis is distributed throughout Shanxi Province, and like samples from Inner Mongolia, the eastern Mediterranean genotype 42 was the main epidemic strain (97%). The HOOF-printing showed a higher diversity than MLVA-16 with a genetic similarity coefficient ranging from 56.8% to 100%.Conclusions
According to the MLVA-16 and HOOF-printing results, both methods could be used for the epidemiological surveillance of brucellosis. A new genotype was found in both Shanxi and Guangdong Provinces. In areas with brucellosis, the MLVA-16 scheme is very important for tracing cases back to their origins during outbreak investigations. It may facilitate the expansion and eradication of the disease. 相似文献62.
63.
Masato Yuasa Tsuyoshi Yamada Takashi Taniyama Tomokazu Masaoka Wei Xuetao Toshitaka Yoshii Masaki Horie Hiroaki Yasuda Toshimasa Uemura Atsushi Okawa Shinichi Sotome 《PloS one》2015,10(2)
We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2.Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2. 相似文献
64.
MicroRNAs can function as key tumor suppressors or oncogenes and act as biomarkers for cancer diagnosis or prognosis. Although high-throughput assays have revealed many miRNA biomarkers for pancreatic ductal adenocarcinoma (PDAC), only a few have been validated in independent populations or investigated for functional significance in PDAC pathogenesis. In this study, we correlated the expression of 36 potentially prognostic miRNAs within PDAC tissue with clinico-pathological features and survival in 151 Chinese patients. We then analyzed the functional roles and target genes of two miRNAs in PDAC development. We found that high expression of miR-186 and miR-326 predict poor and improved survival, respectively. miR-186 was over-expressed in PDAC patients compared with controls, especially in patients with large tumors (>2 cm), lymph node metastasis, or short-term survival (< 24 months). In contrast, miR-326 was down-regulated in patients compared with controls and displayed relatively increased expression in the patients with long-term survival or without venous invasion. Functional experiments revealed that PDAC cell proliferation and migration was decreased following inhibition and enhanced following over-expression of miR-186. In contrast, it was enhanced following inhibition and decreased after over-expression of miR-326. A luciferase assay indicated that miR-186 can bind directly to the 3′-UTR of NR5A2 to repress gene expression. These findings suggest that miR-186 over-expression contributes to the invasive potential of PDAC, likely via suppression of NR5A2, thereby leading to a poor prognosis; high miR-326 expression prolongs survival likely via the decreasing invasive potential of PDAC cells. These two miRNAs can be used as markers for clinical diagnosis and prognosis, and they represent therapeutic targets for PDAC. 相似文献
65.
Homologous recombination and non-homologous end joining are two major DNA double-strand-break repair pathways. While HR-mediated repair requires a homologous sequence as the guiding template to restore the damage site precisely, NHEJ-mediated repair ligates the DNA lesion directly and increases the risk of losing nucleotides. Therefore, how a cell regulates the balance between HR and NHEJ has become an important issue for maintaining genomic integrity over time. Here we report that SIRT1-dependent KAP1 deacetylation positively regulates NHEJ. We show that up-regulation of KAP1 attenuates HR efficiency while promoting NHEJ repair. Moreover, SIRT1-mediated KAP1 deacetylation further enhances the effect of NHEJ by stabilizing its interaction with 53BP1, which leads to increased 53BP1 focus formation in response to DNA damage. Taken together, our study suggests a SIRT1-KAP1 regulatory mechanism for HR-NHEJ repair pathway choice. 相似文献
66.
Gang Pei Laura Schnettger Marc Bronietzki Urska Repnik Gareth Griffiths Maximiliano Gabriel Gutierrez 《Molecular biology of the cell》2015,26(17):3061-3070
Little is known about the molecular players that regulate changes in the endocytic pathway during immune activation. Here we investigate the role of Rab20 in the endocytic pathway during activation of macrophages. Rab20 is associated with endocytic structures, but the function of this Rab GTPase in the endocytic pathway remains poorly characterized. We find that in macrophages, Rab20 expression and endosomal association significantly increase after interferon-γ (IFN-γ) treatment. Moreover, IFN-γ and Rab20 expression induce a dramatic enlargement of endosomes. These enlarged endosomes are the result of homotypic fusion promoted by Rab20 expression. The expression of Rab20 or the dominant-negative mutant Rab20T19N does not affect transferrin or dextran 70 kDa uptake. However, knockdown of Rab20 accelerates epidermal growth factor (EGF) trafficking to LAMP-2–positive compartments and EGF receptor degradation. Thus this work defines a function for Rab20 in the endocytic pathway during immune activation of macrophages. 相似文献
67.
Jing Yu Yun Kong Suqin Gao Lihong Miao Pei Zou Bo Xu Chi Zeng Xiaolin Zhang 《Journal of applied phycology》2015,27(3):1213-1221
68.
Involvement of OsPht1;4 in phosphate acquisition and mobilization facilitates embryo development in rice 总被引:4,自引:0,他引:4 下载免费PDF全文
Fang Zhang Yafei Sun Wenxia Pei Ajay Jain Rui Sun Yue Cao Xueneng Wu Tingting Jiang Liang Zhang Xiaorong Fan Aiqun Chen Qirong Shen Guohua Xu Shubin Sun 《The Plant journal : for cell and molecular biology》2015,82(4):556-569
Phosphate (Pi) transporters mediate acquisition and transportation of Pi within plants. Here, we investigated the functions of OsPht1;4 (OsPT4), one of the 13 members of the Pht1 family in rice. Quantitative real‐time RT‐PCR analysis revealed strong expression of OsPT4 in roots and embryos, and OsPT4 promoter analysis using reporter genes confirmed these findings. Analysis using rice protoplasts showed that OsPT4 localized to the plasma membrane. OsPT4 complemented a yeast mutant defective in Pi uptake, and also facilitated increased accumulation of Pi in Xenopus oocytes. Further, OsPT4 genetically modified (GM) rice lines were generated by knockout/knockdown or over‐expression of OsPT4. Pi concentrations in roots and shoots were significantly lower and higher in knockout/knockdown and over‐expressing plants, respectively, compared to wild‐type under various Pi regimes. 33Pi uptake translocation assays corroborated the altered acquisition and mobilization of Pi in OsPT4 GM plants. We also observed effects of altered expression levels of OsPT4 in GM plants on the concentration of Pi, the size of the embryo, and several attributes related to seed development. Overall, our results suggest that OsPT4 encodes a plasma membrane‐localized Pi transporter that facilitates acquisition and mobilization of Pi, and also plays an important role in development of the embryo in rice. 相似文献
69.
70.