全文获取类型
收费全文 | 3789篇 |
免费 | 269篇 |
国内免费 | 2篇 |
出版年
2023年 | 15篇 |
2022年 | 31篇 |
2021年 | 71篇 |
2020年 | 60篇 |
2019年 | 81篇 |
2018年 | 114篇 |
2017年 | 100篇 |
2016年 | 160篇 |
2015年 | 258篇 |
2014年 | 264篇 |
2013年 | 311篇 |
2012年 | 326篇 |
2011年 | 331篇 |
2010年 | 219篇 |
2009年 | 194篇 |
2008年 | 229篇 |
2007年 | 222篇 |
2006年 | 199篇 |
2005年 | 186篇 |
2004年 | 174篇 |
2003年 | 141篇 |
2002年 | 140篇 |
2001年 | 50篇 |
2000年 | 27篇 |
1999年 | 21篇 |
1998年 | 30篇 |
1997年 | 13篇 |
1996年 | 19篇 |
1995年 | 8篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1966年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有4060条查询结果,搜索用时 15 毫秒
41.
Ruiyu Xie Logan J. Everett Hee-Woong Lim Nisha A. Patel Jonathan Schug Evert Kroon Olivia G. Kelly Allen Wang Kevin A. D’Amour Allan J. Robins Kyoung-Jae Won Klaus H. Kaestner Maike Sander 《Cell Stem Cell》2013,12(2):224-237
Highlights? Pancreatic lineage progression is governed by PcG-dependent chromatin remodeling ? A temporal chromatin signature predicts regulators of pancreatic development ? Endocrine cells differentiated from hESCs in vivo are similar to native human islets ? In vitro-produced malfunctioning endocrine cells exhibit aberrant chromatin structure 相似文献
42.
Jin-Su Kim Daekee Kwon Seung-Taeh Hwang Dong Ryul Lee Sung Han Shim Hee-Chun Kim Hansoo Park Won Kim Myung-Kwan Han Soo-Hong Lee 《PloS one》2013,8(7)
Background
Human embryonic stem cells (hESCs) are a promising and powerful source of cells for applications in regenerative medicine, tissue engineering, cell-based therapies, and drug discovery. Many researchers have employed conventional culture techniques using feeder cells to expand hESCs in significant numbers, although feeder-free culture techniques have recently been developed. In regard to stem cell expansion, gap junctional intercellular communication (GJIC) is thought to play an important role in hESC survival and differentiation. Indeed, it has been reported that hESC-hESC communication through connexin 43 (Cx43, one of the major gap junctional proteins) is crucial for the maintenance of hESC stemness during expansion. However, the role of GJIC between hESCs and feeder cells is unclear and has not yet been reported.Methodology/Principal Findings
This study therefore examined whether a direct Cx43-mediated interaction between hESCs and human adipose-derived stem cells (hASCs) influences the maintenance of hESC stemness. Over 10 passages, hESCs cultured on a layer of Cx43-downregulated hASC feeder cells showed normal morphology, proliferation (colony growth), and stemness, as assessed by alkaline phosphatase (AP), OCT4 (POU5F1-Human gene Nomenclature Database), SOX2, and NANOG expression.Conclusions/Significance
These results demonstrate that Cx43-mediated GJIC between hESCs and hASC feeder cells is not an important factor for the conservation of hESC stemness and expansion. 相似文献43.
Huaiwei Liu Yuanzhang Sun Kristine Rose M. Ramos Grace M. Nisola Kris Ni?o G. Valdehuesa Won–Keun Lee Si Jae Park Wook-Jin Chung 《PloS one》2013,8(12)
Embden-Meyerhof pathway (EMP) in tandem with 2-C-methyl-D-erythritol 4-phosphate pathway (MEP) is commonly used for isoprenoid biosynthesis in E. coli. However, this combination has limitations as EMP generates an imbalanced distribution of pyruvate and glyceraldehyde-3-phosphate (G3P). Herein, four glycolytic pathways—EMP, Entner-Doudoroff Pathway (EDP), Pentose Phosphate Pathway (PPP) and Dahms pathway were tested as MEP feeding modules for isoprene production. Results revealed the highest isoprene production from EDP containing modules, wherein pyruvate and G3P were generated simultaneously; isoprene titer and yield were more than three and six times higher than those of the EMP module, respectively. Additionally, the PPP module that generates G3P prior to pyruvate was significantly more effective than the Dahms pathway, in which pyruvate production precedes G3P. In terms of precursor generation and energy/reducing-equivalent supply, EDP+PPP was found to be the ideal feeding module for MEP. These findings may launch a new direction for the optimization of MEP-dependent isoprenoid biosynthesis pathways. 相似文献
44.
45.
Jung Ok Park Do‐Young Choi Dong‐Sic Choi Hee Joung Kim Jeong Won Kang Jae Hun Jung Jeong Hwa Lee Jayoung Kim Michael R. Freeman Kye Young Lee Yong Song Gho Kwang Pyo Kim 《Proteomics》2013,13(14):2125-2134
Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano‐LC–MS/MS following 1D SDS‐PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung‐enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC. 相似文献
46.
Dong Hoon Shin Gyeong Im Yu Jae Seok Hwang Eun Soo Kim Jong Won Yun 《Proteomics》2013,13(15):2361-2374
In the present study, we screened proteomic and cytokine biomarkers between patients with adenomatous polyps and colorectal cancer (CRC) in order to improve our understanding of the molecular mechanisms behind turmorigenesis and tumor progression in CRC. To this end, we performed comparative proteomic analysis of plasma proteins using a combination of 2DE and MS as well as profiled differentially regulated cytokines and chemokines by multiplex bead analysis. Proteomic analysis identified 11 upregulated and 13 downregulated plasma proteins showing significantly different regulation patterns with diagnostic potential for predicting progression from adenoma to carcinoma. Some of these proteins have not previously been implicated in CRC, including upregulated leucine‐rich α‐2‐glycoprotein, hemoglobin subunit β, Ig α‐2 chain C region, and complement factor B as well as downregulated afamin, zinc‐α‐2‐glycoprotein, vitronectin, and α‐1‐antichymotrypsin. In addition, plasma levels of three cytokines/chemokines, including interleukin‐8, interferon gamma‐induced protein 10, and tumor necrosis factor α, were remarkably elevated in patients with CRC compared to those with adenomatous polyps. Although further clinical validation is required, these proteins and cytokines can be established as novel biomarkers for CRC and/or its progression from colon adenoma. 相似文献
47.
Sajeesh Kappachery Jae Woong Yu Gangadhar Baniekal-Hiremath Se Won Park 《Comptes rendus biologies》2013,336(11-12):530-545
Identification of major stress tolerance genes of a crop plant is important for the rapid development of its stress-tolerant cultivar. Here, we used a yeast functional screen method to identify potential drought-tolerance genes from a potato plant. A cDNA expression library was constructed from hyperosmotic stressed potato plants. The yeast transformants expressing different cDNAs were selected for their ability to survive in hyperosmotic stress conditions. The relative tolerances of the selected yeast transformants to multiple abiotic stresses were also studied. Specific potato cDNAs expressed in the tolerant yeast transformants were identified. Sixty-nine genes were found capable of enhancing hyperosmotic stress tolerance of yeast. Based on the relative tolerance data generated, 12 genes were selected, which could be most effective in imparting higher drought tolerance to potato with better survival in salt and high-temperature stresses. Orthologues of few genes identified here are previously known to increase osmotic stress tolerance of yeast and plants; however, specific studies are needed to confirm their role in the osmotic stress tolerance of potato. 相似文献
48.
Daemin Kim Kevin W. Conway Hyung-Bae Jeon Ye-Seul Kwon Yong-Jin Won 《Conservation Genetics》2013,14(4):757-769
The dwarf loach, Kichulchoia brevifasciata, is a primary freshwater fish endemic to South Korea (Republic of Korea). Due to its limited geographic range, special habitat requirements, and scarcity, this species has been considered one of the most endangered cobitid loaches in the world. Gene tree and species tree reconstruction derived from mitochondrial and nuclear sequence data supports the exclusivity of K. brevifasciata and the existence of two highly distinct genetic lineages (eastern and western lineages). Intraspecific genetic variation based on the corrected genetic distance ranged from 0.0013 to 0.0017 (cytochrome b) and 0–0.0012 (nuclear loci) within each lineage and 0.0349 (cytochrome b) and 0.0037–0.0104 (nuclear loci) between the lineages. Although morphologically homogeneous, eastern and western lineages were estimated to have diverged roughly 2.79 million years ago (4.25–1.42, 95 % HPD). Future conservation efforts for K. brevifasciata should consider these genetically distinct lineages as separate evolutionary entities and adopt conservation efforts accordingly. 相似文献
49.
Sona Rajakumari Jun Wu Jeff Ishibashi Hee-Woong Lim An-Hoa Giang Kyoung-Jae Won Randall R. Reed Patrick Seale 《Cell metabolism》2013,17(4):562-574
Highlights? Ebf2 is selectively expressed in brown relative to white adipocytes and binds to chromatin at brown fat-specific target sites of Pparγ ? Ebf2 expression in white fat or muscle precursor cells recruits Pparγ to its brown fat-specific gene targets and drives a complete program of brown adipocyte differentiation ? Brown adipose cells and tissue from Ebf2-deficient mice display a complete loss of thermogenic characteristics while gaining molecular attributes of white adipose 相似文献