全文获取类型
收费全文 | 1940篇 |
免费 | 130篇 |
出版年
2023年 | 3篇 |
2022年 | 19篇 |
2021年 | 32篇 |
2020年 | 16篇 |
2019年 | 22篇 |
2018年 | 32篇 |
2017年 | 13篇 |
2016年 | 51篇 |
2015年 | 102篇 |
2014年 | 96篇 |
2013年 | 116篇 |
2012年 | 162篇 |
2011年 | 162篇 |
2010年 | 110篇 |
2009年 | 87篇 |
2008年 | 88篇 |
2007年 | 109篇 |
2006年 | 80篇 |
2005年 | 87篇 |
2004年 | 109篇 |
2003年 | 80篇 |
2002年 | 83篇 |
2001年 | 49篇 |
2000年 | 44篇 |
1999年 | 43篇 |
1998年 | 22篇 |
1997年 | 18篇 |
1996年 | 19篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 21篇 |
1991年 | 17篇 |
1990年 | 12篇 |
1989年 | 20篇 |
1988年 | 14篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 3篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1975年 | 11篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1966年 | 2篇 |
排序方式: 共有2070条查询结果,搜索用时 173 毫秒
61.
Jong Bae Seo Seung-Ryoung Jung Bertil Hille Duk-Su Koh 《Cell biology and toxicology》2016,32(3):229-247
Extracellular adenosine-5′-triphosphate (ATP) regulates cell death and survival of neighboring cells. The detailed effects are diverse depending on cell types and extracellular ATP concentration. We addressed the effect of ATP on ethanol-induced cytotoxicity in epithelial cells, the cell type that experiences the highest concentrations of alcohol. Using pancreatic duct epithelial cells (PDEC), we found that a micromolar range of ATP reverses all intracellular toxicity mechanisms triggered by exceptionally high doses of ethanol and, thus, improves cell viability dramatically. Out of the many purinergic receptors expressed in PDEC, the P2Y1 receptor was identified to mediate the protective effect, based on pharmacological and siRNA assays. Activation of P2Y1 receptors increased intracellular cyclic adenosine monophosphate (cAMP). The protective effect of ATP was mimicked by forskolin and 8-Br-cAMP but inhibited by a protein kinase A (PKA) inhibitor, H-89. Finally, ATP reverted leakiness of PDEC monolayers induced by ethanol and helped to maintain epithelial integrity. We suggest that purinergic receptors reduce extreme alcohol-induced cell damage via the cAMP signal pathway in PDEC and some other types of cells. 相似文献
62.
63.
64.
65.
Jungil Yang Lae‐Hyeon Cho Jinmi Yoon Hyeryung Yoon Antt Htet Wai Woo‐Jong Hong Muho Han Hitoshi Sakakibara Wanqi Liang Ki‐Hong Jung Jong‐Seong Jeon Hee‐Jong Koh Dabing Zhang Gynheung An 《Plant biotechnology journal》2019,17(1):178-187
Grain number is an important agronomic trait. We investigated the roles of chromatin interacting factor Oryza sativa VIN3‐LIKE 2 (OsVIL2), which controls plant biomass and yield in rice. Mutations in OsVIL2 led to shorter plants and fewer grains whereas its overexpression (OX) enhanced biomass production and grain numbers when compared with the wild type. RNA‐sequencing analyses revealed that 1958 genes were up‐regulated and 2096 genes were down‐regulated in the region of active division within the first internodes of OX plants. Chromatin immunoprecipitation analysis showed that, among the downregulated genes, OsVIL2 was directly associated with chromatins in the promoter region of CYTOKININ OXIDASE/DEHYDROGENASE2 (OsCKX2), a gene responsible for cytokinin degradation. Likewise, active cytokinin levels were increased in the OX plants. We conclude that OsVIL2 improves the production of biomass and grain by suppressing OsCKX2 chromatin. 相似文献
66.
Takashi Yazawa Yoshitaka Imamichi Koh‐ichi Yuhki Junsuke Uwada Daisuke Mikami Masayuki Shimada Kaoru Miyamoto Takeshi Kitano Satoru Takahashi Toshio Sekiguchi Nobuo Suzuki Md. Rafiqul Islam Khan Fumitaka Ushikubi Akihiro Umezawa Takanobu Taniguchi 《Molecular reproduction and development》2019,86(7):786-797
67.
Liu P Sudhaharan T Koh RM Hwang LC Ahmed S Maruyama IN Wohland T 《Biophysical journal》2007,93(2):684-698
Single wavelength fluorescence cross-correlation spectroscopy (SW-FCCS), introduced to study biomolecular interactions, has recently been reported to monitor enzyme activity by using a newly developed fluorescent protein variant together with cyan fluorescent protein. Here, for the first time to our knowledge, SW-FCCS is applied to detect interactions between membrane receptors in vivo by using the widely used enhanced green fluorescent protein and monomeric red fluorescent protein. The biological system studied here is the epidermal growth factor/ErbB receptor family, which plays pivotal roles in the development of organisms ranging from worms to humans. It is widely thought that a ligand binds to the monomeric form of the receptor and induces its dimeric form for activation. By using SW-FCCS and F?rster resonance energy transfer, we show that the epidermal growth factor receptor and ErbB2 have preformed homo- and heterodimeric structures on the cell surface and quantitation of dimer fractions is performed by SW-FCCS. These receptors are major targets of anti-cancer drug development, and the receptors' homo- and heterodimeric structures are relevant for such developments. 相似文献
68.
69.
Mesenchymal stromal cells (MSCs) have proven useful for cell and immune therapy, but the molecular constituents responsible for their functionalities, in particular, those on the plasma membrane, remain largely unknown. Here we employed both gel and nongel based MS to analyze human MSCs' membrane proteome before and after adipogenesis. 2-DE of cells that were pretreated with membrane impermeable fluorescent dyes revealed that both the whole cell proteome and the cell surface subproteome were independent of donors. LC coupled with tandem MS analysis of the plasma membrane-containing fraction allowed us to identify 707 proteins, approximately half of which could be annotated as membrane-related proteins. Of particular interest was a subset of ectodomain-containing membrane-bound proteins that encompass most known surface markers for MSCs, but also contain a multitude of solute carriers and ATPases. Upon adipogenic differentiation, this proteomic profile was amended to include several proteins involved in lipid metabolism and trafficking, at the expense of, most noticeably, ectoenzymes. Our results here provide not only a basis for future studies of MSC-specific molecular mechanisms, but also a molecular inventory for the development of antibody-based cell isolation and identification procedures. 相似文献
70.
Davis GE Koh W Stratman AN 《Birth defects research. Part C, Embryo today : reviews》2007,81(4):270-285
Recent data have revealed new mechanisms that underlie endothelial cell (EC) lumen formation during vascular morphogenic events in development, wound repair, and other disease states. It is apparent that EC interactions with extracellular matrices (ECMs) establish signaling cascades downstream of integrin ligation leading to activation of the Rho GTPases, Cdc42 and Rac1, which are required for lumen formation. In large part, this process is driven by intracellular vacuole formation and coalescence, which rapidly leads to the creation of fluid-filled matrix-free spaces that are then interconnected via EC-EC interactions to create multicellular tube structures. EC vacuoles markedly accumulate in a polarized fashion directly adjacent to the centrosome in a region that strongly accumulates Cdc42 protein as indicated by green fluorescent protein (GFP)-Cdc42 during the lumen formation process. Downstream of Cdc42-mediated signaling, key molecules that have been identified to be required for EC lumen formation include Pak2, Pak4, Par3, Par6, and the protein kinase C (PKC) isoforms zeta and epsilon. Together, these molecules coordinately regulate the critical EC lumen formation process in three-dimensional (3D) collagen matrices. These events also require cell surface proteolysis mediated through membrane type 1 matrix metalloproteinase (MT1-MMP), which is necessary to create vascular guidance tunnels within the 3D matrix environment. These tunnels represent physical spaces within the ECM that are necessary to regulate vascular morphogenic events, including the establishment of interconnected vascular tube networks as well as the recruitment of pericytes to initiate vascular tube maturation (via basement membrane matrix assembly) and stabilization. Current research continues to analyze how specific molecules integrate signaling information in concert to catalyze EC lumen formation, pericyte recruitment, and stabilization processes to control vascular morphogenesis in 3D extracellular matrices. 相似文献