全文获取类型
收费全文 | 1210篇 |
免费 | 93篇 |
专业分类
1303篇 |
出版年
2023年 | 5篇 |
2022年 | 9篇 |
2021年 | 21篇 |
2020年 | 15篇 |
2019年 | 17篇 |
2018年 | 25篇 |
2017年 | 29篇 |
2016年 | 33篇 |
2015年 | 49篇 |
2014年 | 61篇 |
2013年 | 60篇 |
2012年 | 86篇 |
2011年 | 92篇 |
2010年 | 58篇 |
2009年 | 35篇 |
2008年 | 69篇 |
2007年 | 68篇 |
2006年 | 56篇 |
2005年 | 74篇 |
2004年 | 73篇 |
2003年 | 58篇 |
2002年 | 52篇 |
2001年 | 25篇 |
2000年 | 18篇 |
1999年 | 24篇 |
1998年 | 17篇 |
1997年 | 6篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 4篇 |
1992年 | 16篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 17篇 |
1987年 | 11篇 |
1986年 | 8篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1970年 | 8篇 |
1969年 | 4篇 |
1967年 | 4篇 |
排序方式: 共有1303条查询结果,搜索用时 15 毫秒
41.
Kazumi Hirano Toin H. Van Kuppevelt Shoko Nishihara 《Biochemical and biophysical research communications》2013,430(3):1175-1181
The characteristics of pluripotent embryonic stem cells of human and mouse are different. The properties of human embryonic stem cells (hESCs) are similar to those of mouse epiblast stem cells (mEpiSCs), which are in a later developmental pluripotency state, the so-called “primed state” compared to mouse embryonic stem cells (mESCs) which are in a naïve state. As a result of the properties of the primed state, hESCs proliferate slowly, cannot survive as single cells, and can only be transfected with genes at low efficiency. Generating hESCs in the naïve state is necessary to overcome these problems and allow their application in regenerative medicine. Therefore, clarifying the mechanism of the transition between the naïve and primed states in pluripotent stem cells is important for the establishment of stable methods of generating naïve state hESCs. However, the signaling pathways which contribute to the transition between the naïve and primed states are still unclear. In this study, we carried out induction from mESCs to mEpiSC-like cells (mEpiSCLCs), and observed an increase in the activation of Fas signaling during the induction. The expression of Fgf5, an epiblast marker, was diminished by inhibition of Fas signaling using the caspase-8 and -3 blocking peptides, IETD and DEVD, respectively. Furthermore, during the induction, we observed increased expression of 3-O sulfated heparan sulfate (HS) structures synthesized by HS 3-O-sulfotransferase (3OST), which are recognized by the HS4C3 antibody (HS4C3-binding epitope). Knockdown of 3OST-5 reduced Fas signaling and the potential for the transition to mEpiSCLCs. This indicates that the HS4C3-binding epitope is necessary for the transition to the primed state. We propose that Fas signaling through the HS4C3-binding epitope contributes to the transition from the naïve state to the primed state. 相似文献
42.
43.
44.
Natalia J. Martinez Ganesha Rai Adam Yasgar Wendy A. Lea Hongmao Sun Yuhong Wang Diane K. Luci Shyh-Ming Yang Kana Nishihara Shunichi Takeda Mohiuddin Irina Earnshaw Tetsuya Okada Kazutoshi Mori Kelli Wilson Gregory J. Riggins Menghang Xia Maurizio Grimaldi Ajit Jadhav David J. Maloney Anton Simeonov 《PloS one》2016,11(11)
45.
Akiko Shibui Ayako Takamori Mohammed E.M. Tolba Aya Nambu Eri Shimura Sachiko Yamaguchi Chizu Sanjoba Hajime Suto Katsuko Sudo Ko Okumura Sumio Sugano Hideaki Morita Hirohisa Saito Kenji Matsumoto Susumu Nakae 《Biochemistry and Biophysics Reports》2016
IL-25, IL-33 and TSLP, which are produced predominantly by epithelial cells, can induce production of Th2-type cytokines such as IL-4, IL-5 and/or IL-13 by various types of cells, suggesting their involvement in induction of Th2-type cytokine-associated immune responses. It is known that Th2-type cytokines contribute to host defense against malaria parasite infection in mice. However, the roles of IL-25, IL-33 and TSLP in malaria parasite infection remain unclear. Thus, to elucidate this, we infected wild-type, IL-25?/?, IL-33?/? and TSLP receptor (TSLPR)?/? mice with Plasmodium berghei (P. berghei) ANKA, a murine malaria strain. The expression levels of IL-25, IL-33 and TSLP mRNA were changed in the brain, liver, lung and spleen of wild-type mice after infection, suggesting that these cytokines are involved in host defense against P. berghei ANKA. However, the incidence of parasitemia and survival in the mutant mice were comparable to in the wild-type mice. These findings indicate that IL-25, IL-33 and TSLP are not critical for host defense against P. berghei ANKA. 相似文献
46.
Many plants have mutualistic relationships with ants, whereby plants provide food and/or nesting sites for the symbiotic ants, and in turn the ants protect the host plants by excluding herbivores. While the ants are useful as guards, they may negatively affect host reproduction by excluding pollinators. Here we studied this potential conflict in the myrmecophytic Macaranga winkleri pollinated by the thrips Dolichothrips fialae. Behavioural responses of ant guards to pollinator thrips and their chemicals, and related chemical analyses, provide evidence that thrips deter ant-guards by secreting droplets containing ant-repelling n-decanoic acid from their anuses. This is the first report of insect pollinators repelling their host’s symbiotic guard ants to perform pollination. This is a novel strategy by which a plant host avoids interference with pollination by ant-guards in an ant–plant mutualism. The acquisition of a pollination system that is resistant to ant attacks may have facilitated the evolution of myrmecophytes in the genus Macaranga. 相似文献
47.
Cohesin is a ring‐shaped protein complex that plays a crucial role in sister chromatid cohesion and gene expression. The dynamic association of cohesin with chromatin is essential for these functions. However, the exact nature of cohesin dynamics, particularly cohesin translocation, remains unclear. We evaluated the dynamics of individual cohesin molecules on DNA and found that the cohesin core complex possesses an intrinsic ability to traverse DNA in an adenosine triphosphatase (ATPase)‐dependent manner. Translocation ability is suppressed in the presence of Wapl‐Pds5 and Sororin; this suppression is alleviated by the acetylation of cohesin and the action of mitotic kinases. In Xenopus laevis egg extracts, cohesin is translocated on unreplicated DNA in an ATPase‐ and Smc3 acetylation‐dependent manner. Cohesin movement changes from bidirectional to unidirectional when cohesin faces DNA replication; otherwise, it is incorporated into replicating DNA without being translocated or is dissociated from replicating DNA. This study provides insight into the nature of individual cohesin dynamics and the mechanisms by which cohesin achieves cohesion in different chromatin contexts. 相似文献
48.
Yosuke Kanno Akira Ishisaki Eri Kawashita Hiromi Kuretake Kanako Ikeda Osamu Matsuo 《International journal of biological sciences》2016,12(1):63-71
Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis-caused bone destruction, results from an increase of bone-resorbing osteoclasts (OCs) induced by inflammation. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated that the effect of urokinase-type plasminogen activator (uPA) on inflammatory osteoclastogenesis induced by lipopolysaccharide (LPS), which is a potent stimulator of bone resorption in inflammatory diseases. We found that the uPA deficiency promoted inflammatory osteoclastogenesis and bone loss induced by LPS. We also showed that LPS induced the expression of uPA, and the uPA treatment attenuated the LPS-induced inflammatory osteoclastogenesis of RAW264.7 mouse monocyte/macrophage lineage cells. Additionally, we showed that the uPA-attenuated inflammatory osteoclastgenesis is associated with the activation of plasmin/protease-activated receptor (PAR)-1 axis by uPA. Moreover, we examined the mechanism underlying the effect of uPA on inflammatory osteoclastogenesis, and found that uPA/plasmin/PAR-1 activated the adenosine monophosphate-activated protein kinase (AMPK) pathway through Ca2+/calmodulin dependent protein kinase kinase (CaMKK) activation, and attenuated inflammatory osteoclastogenesis by inactivation of NF-κB in RAW264.7 cells. These data suggest that uPA attenuated inflammatory osteoclastogenesis through the plasmin/PAR-1/Ca2+/CaMKK/AMPK axis. Our findings may provide a novel therapeutic approach to bone loss caused by inflammatory diseases. 相似文献
49.
Efficient modification of the myostatin gene in porcine somatic cells and generation of knockout piglets 下载免费PDF全文
50.
Murakami Shinsuke Nakatani Jun Nakajima Kenichi Amasawa Eri Ii Ryota Hayashi Kiyotada Yoshikawa Naoki Daigo Ichiro Kishita Yusuke Ihara Tomohiko Shobatake Koichi Kudoh Yuki Motoshita Masaharu Kanemoto Keiichiro Hara Minako Kashiwagi Aiichiro Hashimoto Seiji Shigetomi Yosuke Kanzaki Masayuki Kikuchi Yasunori Ohno Hajime Fukushima Yasuhiro 《The International Journal of Life Cycle Assessment》2019,24(8):1544-1552
The International Journal of Life Cycle Assessment - 相似文献