全文获取类型
收费全文 | 216篇 |
免费 | 25篇 |
出版年
2021年 | 5篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 16篇 |
2014年 | 4篇 |
2013年 | 15篇 |
2012年 | 12篇 |
2011年 | 8篇 |
2010年 | 10篇 |
2009年 | 6篇 |
2008年 | 15篇 |
2007年 | 13篇 |
2006年 | 14篇 |
2005年 | 7篇 |
2004年 | 10篇 |
2003年 | 7篇 |
2002年 | 10篇 |
2001年 | 5篇 |
2000年 | 10篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有241条查询结果,搜索用时 20 毫秒
1.
2.
Cynthia J. Tsay 《The Yale journal of biology and medicine》2013,86(2):245-254
Julius Wagner-Jauregg, a preeminent Austrian psychiatrist was awarded the Nobel
Prize in Medicine in 1927 for the development of malaria therapy for the
treatment of neurosyphilis, or general paresis of the insane. Despite being only
one of three psychiatrists to win a Nobel Prize, he has faded from public
consciousness and his name recognition pales in comparison to his contemporary
and fellow Austrian, Sigmund Freud. This paper explores his contributions to the
field of biological psychiatry and also touches upon reasons, such as the
growing bioethics movement, his controversial affiliation with the Nazi Party,
and the evolution of neurosyphilis, that explain why Wagner-Jauregg is not more
widely celebrated for his contributions to the field of psychiatry, even though
his malarial treatment could be considered the earliest triumph of biological
psychiatry over psychoanalysis. 相似文献
3.
Feng-Shiun Shie Young-Ji Shiao Chih-Wen Yeh Chien-Hung Lin Tsai-Teng Tzeng Hao-Chieh Hsu Fong-Lee Huang Huey-Jen Tsay Hui-Kang Liu 《PloS one》2015,10(8)
Diabesity-associated metabolic stresses modulate the development of Alzheimer’s disease (AD). For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ) in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson’s correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD. 相似文献
4.
Yin-Kai Chen Hsin-An Hou Jih-Luh Tang Jie-Yang Jhuang Yan-Jun Lai Ming-Cheng Lee Yuan-Yeh Kuo Wen-Chien Chou Chieh-Yu Liu Chung-Wu Lin Shih-Sung Chuang Chien-Yuan Chen Mei-Hsuan Tseng Chi-Fei Huang Ying-Chieh Chiang Fen-Yu Lee Ming-Chih Liu Chia-Wen Liu Ming Yao Shang-Yi Huang Bor-Sheng Ko Szu-Chun Hsu Shang-Ju Wu Woei Tsay Yao-Chang Chen Hwei-Fang Tien 《PloS one》2015,10(3)
Background
Robo4 is involved in hematopoietic stem/progenitor cell homeostasis and essential for tumor angiogenesis. Expression of Robo4 was recently found in solid tumors and leukemia stem cells. However, the clinical implications of Robo4 expression in patients with acute myeloid leukemia (AML) remain unclear.Methods
We investigated the clinical and prognostic relevance of mRNA expression of Robo4 in bone marrow (BM) mononuclear cells from 218 adult patients with de novo AML. We also performed immunohistochemical staining to assess the Robo4 protein expression in the BM biopsy specimens from 30 selected AML patients in the cohort.Results
Higher Robo4 expression was closely associated with lower white blood cell counts, expression of HLA-DR, CD13, CD34 and CD56 on leukemia cells, t(8;21) and ASXL1 mutation, but negatively correlated with t(15;17) and CEBPA mutation. Compared to patients with lower Robo4 expression, those with higher expression had significantly shorter disease-free survival (DFS) and overall survival (OS). This result was confirmed in an independent validation cohort. Furthermore, multivariate analyses showed that higher Robo4 expression was an independent poor prognostic factor for DFS and OS in total cohort and patients with intermediate-risk cytogenetics, irrespective of age, WBC count, karyotype, and mutation status of NPM1/FLT3-ITD, and CEBPA.Conclusions
BM Robo4 expression can serve as a new biomarker to predict clinical outcomes in AML patients and Robo4 may serve as a potential therapeutic target in patients with higher Robo4 expression. 相似文献5.
6.
Alan Y-L Lee San-San Tsay Mao-Yen Chen Shih-Hsiung Wu 《European journal of biochemistry》2004,271(4):834-844
A gene encoding thermostable Lon protease from Brevibacillus thermoruber WR-249 was cloned and characterized. The Br. thermoruber Lon gene (Bt-lon) encodes an 88 kDa protein characterized by an N-terminal domain, a central ATPase domain which includes an SSD (sensor- and substrate-discrimination) domain, and a C-terminal protease domain. The Bt-lon is a heat-inducible gene and may be controlled under a putative Bacillus subtilis sigmaA-dependent promoter, but in the absence of CIRCE (controlling inverted repeat of chaperone expression). Bt-lon was expressed in Escherichia coli, and its protein product was purified. The native recombinant Br. thermoruber Lon protease (Bt-Lon) displayed a hexameric structure. The optimal temperature of ATPase activity for Bt-Lon was 70 degrees C, and the optimal temperature of peptidase and DNA-binding activities was 50 degrees C. This implies that the functions of Lon protease in thermophilic bacteria may be switched, depending on temperature, to regulate their physiological needs. The peptidase activity of Bt-Lon increases substantially in the presence of ATP. Furthermore, the substrate specificity of Bt-Lon is different from that of E. coli Lon in using fluorogenic peptides as substrates. Notably, the Bt-Lon protein shows chaperone-like activity by preventing aggregation of denatured insulin B-chain in a dose-dependent and ATP-independent manner. In thermal denaturation experiments, Bt-Lon was found to display an indicator of thermostability value, Tm of 71.5 degrees C. Sequence comparison with mesophilic Lon proteases shows differences in the rigidity, electrostatic interactions, and hydrogen bonding of Bt-Lon relevant to thermostability. 相似文献
7.
Shu-Chun Fan Choun-Sea Lin Po-Kai Hsu Shan-Hua Lin Yi-Fang Tsay 《The Plant cell》2009,21(9):2750-2761
Several quantitative trait locus analyses have suggested that grain yield and nitrogen use efficiency are well correlated with nitrate storage capacity and efficient remobilization. This study of the Arabidopsis thaliana nitrate transporter NRT1.7 provides new insights into nitrate remobilization. Immunoblots, quantitative RT-PCR, β-glucuronidase reporter analysis, and immunolocalization indicated that NRT1.7 is expressed in the phloem of the leaf minor vein and that its expression levels increase coincidentally with the source strength of the leaf. In nrt1.7 mutants, more nitrate was present in the older leaves, less 15NO3− spotted on old leaves was remobilized into N-demanding tissues, and less nitrate was detected in the phloem exudates of old leaves. These data indicate that NRT1.7 is responsible for phloem loading of nitrate in the source leaf to allow nitrate transport out of older leaves and into younger leaves. Interestingly, nrt1.7 mutants showed growth retardation when external nitrogen was depleted. We conclude that (1) nitrate itself, in addition to organic forms of nitrogen, is remobilized, (2) nitrate remobilization is important to sustain vigorous growth during nitrogen deficiency, and (3) source-to-sink remobilization of nitrate is mediated by phloem. 相似文献
8.
Video-rate scanning two-photon excitation fluorescence microscopy and ratio imaging with cameleons 总被引:10,自引:0,他引:10 下载免费PDF全文
A video-rate (30 frames/s) scanning two-photon excitation microscope has been successfully tested. The microscope, based on a Nikon RCM 8000, incorporates a femtosecond pulsed laser with wavelength tunable from 690 to 1050 nm, prechirper optics for laser pulse-width compression, resonant galvanometer for video-rate point scanning, and a pair of nonconfocal detectors for fast emission ratioing. An increase in fluorescent emission of 1.75-fold is consistently obtained with the use of the prechirper optics. The nonconfocal detectors provide another 2.25-fold increase in detection efficiency. Ratio imaging and optical sectioning can therefore be performed more efficiently without confocal optics. Faster frame rates, at 60, 120, and 240 frames/s, can be achieved with proportionally reduced scan lines per frame. Useful two-photon images can be acquired at video rate with a laser power as low as 2.7 mW at specimen with the genetically modified green fluorescent proteins. Preliminary results obtained using this system confirm that the yellow "cameleons" exhibit similar optical properties as under one-photon excitation conditions. Dynamic two-photon images of cardiac myocytes and ratio images of yellow cameleon-2.1, -3.1, and -3.1nu are also presented. 相似文献
9.
Although multiple subtypes of sodium channels are expressed in most neurons, the specific contributions of the individual
sodium channels remain to be studied. The role of zebrafish Nav1.6 sodium channels in the embryonic locomotor movements has been investigated by the antisense morpholino (MO) knockdown.
MO1 and MO2 are targeted at the regions surrounding the translation start site of zebrafish Nav1.6 mRNA. MO3 is targeted at the RNA splicing donor site of exon 2. The correctly spliced Nav1.6 mRNA of MO3 morphants is 6% relative to that of the wild-type embryos. Nav1.6-targeted MO1, MO2 and MO3 attenuate the spontaneous contraction, tactile sensitivity, and swimming in comparison with
a scrambled morpholino and mutated MO3 morpholino. No significant defect is observed in the development of slow muscles, the
axonal projection of primary motoneurons, and neuromuscular junctions. The movement impairments caused by MO1, MO2, and MO3
suggest that the function of Nav1.6 sodium channels is essential on the normal early embryonic locomotor activities. 相似文献
10.
The objectives of this study were to characterize the nuclear and cytoskeletal changes of pig oocytes during in vitro maturation (IVM) and the development of the reconstructed embryos after injection with membrane intact or disintegrated donor cells. Cumulus-oocyte complexes (COCs) were collected from abattoir ovaries by follicle (2-8mm) aspiration. In Experiment 1, COCs were cultured in NCSU-23 medium for 0, 11, 22, 33, and 44 h. Oocytes were fixed at different time points for nuclear and cytoskeletal labeling. Forty-three percent and 75% oocytes progressed to MII stage at 33 and 44 h after IVM culture, respectively. Dynamic shift of spindle and cytoplasmic microtubules was evident. In Experiment 2, matured oocytes were injected with either the whole cumulus cell with or without intact cell membranes after enucleation. The reconstructed oocytes were fixed at 0, 2, or 4 h after cell injection for nuclear and cytoskeletal evaluation. When an intact cumulus cell was injected, the injected cell remained intact within 4h after injection. When a cell with disintegrated membrane was injected, 59-63% (n=146) of the injected cell underwent premature chromosome condensation (PCC). In Experiment 3, the reconstructed pig oocytes received membrane-disintegrated cumulus cells or fetal fibroblasts were cultured in PZM medium. The blastocyst rate of the fibroblast-injected embryos was 10%, which was lower than the non-cloned parthenotes (33%, P<0.05) but higher than the cumulus cell-injected embryos (2.7%). These results suggest that pig oocytes are subjected to nuclear and cytoskeletal reorganization during maturation. Pig oocytes injected with membrane-disintegrated fibroblast cells support better blastocyst development of the cloned embryos. 相似文献