全文获取类型
收费全文 | 3061篇 |
免费 | 155篇 |
出版年
2023年 | 5篇 |
2022年 | 21篇 |
2021年 | 51篇 |
2020年 | 23篇 |
2019年 | 31篇 |
2018年 | 52篇 |
2017年 | 33篇 |
2016年 | 69篇 |
2015年 | 109篇 |
2014年 | 121篇 |
2013年 | 154篇 |
2012年 | 226篇 |
2011年 | 233篇 |
2010年 | 145篇 |
2009年 | 106篇 |
2008年 | 202篇 |
2007年 | 214篇 |
2006年 | 214篇 |
2005年 | 159篇 |
2004年 | 211篇 |
2003年 | 177篇 |
2002年 | 162篇 |
2001年 | 59篇 |
2000年 | 43篇 |
1999年 | 56篇 |
1998年 | 20篇 |
1997年 | 24篇 |
1996年 | 26篇 |
1995年 | 21篇 |
1994年 | 22篇 |
1993年 | 13篇 |
1992年 | 23篇 |
1991年 | 18篇 |
1990年 | 19篇 |
1989年 | 19篇 |
1988年 | 16篇 |
1987年 | 9篇 |
1986年 | 14篇 |
1985年 | 14篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 10篇 |
1976年 | 4篇 |
1973年 | 3篇 |
1971年 | 3篇 |
1970年 | 3篇 |
排序方式: 共有3216条查询结果,搜索用时 15 毫秒
101.
102.
Indirect reciprocity is one of the major mechanisms of the evolution of cooperation. Because constant monitoring and accurate evaluation in moral assessments tend to be costly, indirect reciprocity can be exploited by cost evaders. A recent study crucially showed that a cooperative state achieved by indirect reciprocators is easily destabilized by cost evaders in the case with no supportive mechanism. Here, we present a simple and widely applicable solution that considers pre-assessment of cost evaders. In the pre-assessment, those who fail to pay for costly assessment systems are assigned a nasty image that leads to them being rejected by discriminators. We demonstrate that considering the pre-assessment can crucially stabilize reciprocal cooperation for a broad range of indirect reciprocity models. In particular for the most leading social norms, we analyse the conditions under which a prosocial state becomes locally stable. 相似文献
103.
Youichi Suzuki Wei-Xin Chin Qi'En Han Koji Ichiyama Ching Hua Lee Zhi Wen Eyo Hirotaka Ebina Hirotaka Takahashi Chikako Takahashi Beng Hui Tan Takayuki Hishiki Kenji Ohba Toshifumi Matsuyama Yoshio Koyanagi Yee-Joo Tan Tatsuya Sawasaki Justin Jang Hann Chu Subhash G. Vasudevan Kouichi Sano Naoki Yamamoto 《PLoS pathogens》2016,12(1)
Dengue virus (DENV) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN) response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN). Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), and La motif-related protein 1 (LARP1). Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells. 相似文献
104.
Efficient modification of the myostatin gene in porcine somatic cells and generation of knockout piglets 下载免费PDF全文
105.
'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells 总被引:3,自引:0,他引:3
Okamoto K Miyoshi S Toyoda M Hida N Ikegami Y Makino H Nishiyama N Tsuji H Cui CH Segawa K Uyama T Kami D Miyado K Asada H Matsumoto K Saito H Yoshimura Y Ogawa S Aeba R Yozu R Umezawa A 《Experimental cell research》2007,313(12):2550-2562
The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy. 相似文献
106.
Yamane J Kubo A Nakayama K Yuba-Kubo A Katsuno T Tsukita S Tsukita S 《Experimental cell research》2007,313(16):3472-3485
The small GTPase Rab6 regulates retrograde membrane traffic from endosomes to the Golgi apparatus and from the Golgi to the endoplasmic reticulum (ER). We examined the role of a Rab6-binding protein, TMF/ARA160 (TATA element modulatory factor/androgen receptor-coactivator of 160 kDa), in this process. High-resolution immunofluorescence imaging revealed that TMF signal surrounded Rab6-positive Golgi structures and immunoelectron microscopy revealed that TMF is concentrated at the budding structures localized at the tips of cisternae. The knockdown of either TMF or Rab6 by RNA interference blocked retrograde transport of endocytosed Shiga toxin from early/recycling endosomes to the trans-Golgi network, causing missorting of the toxin to late endosomes/lysosomes. However, the TMF knockdown caused Rab6-dependent displacement of N-acetylgalactosaminyltransferase-2 (GalNAc-T2), but not beta1,4-galactosyltransferase (GalT), from the Golgi. Analyses using chimeric proteins, in which the cytoplasmic regions of GalNAc-T2 and GalT were exchanged, revealed that the cytoplasmic region of GalNAc-T2 plays a crucial role in its TMF-dependent Golgi retention. These observations suggest critical roles for TMF in two Rab6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER. 相似文献
107.
Germain H Houde J Gray-Mitsumune M Sawasaki T Endo Y Rivoal J Matton DP 《FEBS letters》2007,581(26):5137-5142
Solanum chacoense ovule receptor kinase 28 (ScORK28) was found among 30 receptor kinases from an ovule cDNA library enriched for weakly expressed mRNAs. This LRR-RLK displayed high level of tissue specificity at the RNA and protein levels and was predominantly expressed in female reproductive tissues. Protein expression analyses in planta revealed that ScORK28 was N-glycosylated and ScORK28::GFP fusion analyses showed that it was localized at the plasma membrane. Bacterial expression of ScORK28 catalytic domain followed by kinase activity assays revealed that ScORK28 is an active Mg2+-dependent protein kinase and that the juxtamembrane domain is necessary for kinase activity. 相似文献
108.
Anemia is a symptom in patients with Pearson syndrome caused by the accumulation of mutated mitochondrial DNA (mtDNA). Such mutated mtDNAs have been detected in patients with anemia. This suggested that respiration defects due to mutated mtDNA are responsible for the anemia. However, there has been no convincing experimental evidence to confirm the pathophysiological relation between respiration defects in hematopoietic cells and expression of anemia. We address this issue by transplanting bone marrow cells carrying pathogenic mtDNA with a large-scale deletion (ΔmtDNA) into normal mice. The bone marrow-transplanted mice carried high proportion of ΔmtDNA only in hematopoietic cells, and resultant the mice suffered from macrocytic anemia. They show abnormalities of erythroid differentiation and weak erythropoietic response to a stressful condition. These observations suggest that hematopoietic cell-specific respiration defects caused by mtDNAs with pathogenic mutations are responsible for anemia by inducing abnormalities in erythropoiesis. 相似文献
109.
根据http://www.tigr.org中与小麦几丁质酶基因相关的序列TC187877,设计引物,分别从小麦品种Gamenya和苏麦3号中扩增到大小约为1 000bp的片段。经序列测定和软件分析比较,发现这些片段所编码的蛋白质氨基酸序列,都有CHITINASE-19.1和CHITINASE-19.2的基序,为第II类几丁质酶基因。扩增的核酸序列在GenBank上发表,登录号分别为AY973229和AY973230。 相似文献
110.
Sawa T Zaki MH Okamoto T Akuta T Tokutomi Y Kim-Mitsuyama S Ihara H Kobayashi A Yamamoto M Fujii S Arimoto H Akaike T 《Nature chemical biology》2007,3(11):727-735
The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3',5'-cyclic monophosphate (cGMP). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO. 相似文献