全文获取类型
收费全文 | 327篇 |
免费 | 9篇 |
出版年
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 24篇 |
2012年 | 14篇 |
2011年 | 28篇 |
2010年 | 10篇 |
2009年 | 7篇 |
2008年 | 33篇 |
2007年 | 22篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 23篇 |
2003年 | 25篇 |
2002年 | 24篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1985年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有336条查询结果,搜索用时 31 毫秒
31.
Toshio Watanabe Toshihisa Takeuchi Osamu Handa Yasuhisa Sakata Tetsuya Tanigawa Masatsugu Shiba Yuji Naito Kazuhide Higuchi Kazuma Fujimoto Toshikazu Yoshikawa Tetsuo Arakawa 《PloS one》2015,10(4)
Background
Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.Aim
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.Methods
We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.Results
The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.Conclusions
High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.Trial Registration
UMIN Clinical Trials Registry UMIN000003463 相似文献32.
Akira Inoue Naoki Yamamoto Masatsugu Kimura Koji Nishio Hideo Yamane Koichi Nakajima 《FEBS letters》2014
RBM10, originally called S1-1, is a nuclear RNA-binding protein with domains characteristic of RNA processing proteins. It has been reported that RBM10 constitutes spliceosome complexes and that RBM5, a close homologue of RBM10, regulates alternative splicing of apoptosis-related genes, Fas and cFLIP. In this study, we examined whether RBM10 has a regulatory function in splicing similar to RBM5, and determined that it indeed regulates alternative splicing of Fas and Bcl-x genes. RBM10 promotes exon skipping of Fas pre-mRNA as well as selection of an internal 5′-splice site in Bcl-x pre-mRNA. We propose a consensus RBM10-binding sequence at 5′-splice sites of target exons and a mechanistic model of RBM10 action in the alternative splicing. 相似文献
33.
The clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis was investigated. Germline polymorphisms of GSTM1, GSTT1 and p53 codon 72 together with human papillomavirus (HPV) types were examined in a total of 457 blood and cervical smear samples from normal healthy women and the patients with premalignant and malignant cervical lesions. The 167 patients with low-grade squamous intraepithelial lesion (LSIL), 49 with high-grade SIL (HSIL) and 83 with squamous cell carcinoma (SCC) had significantly higher frequency of high-risk HPV than 158 controls. The 49 patients with HSIL and 83 with SCC had statistically higher frequency of null GSTT1 genotype than 158 controls. There was an increased odds ratio for null GSTT1 genotype in HSIL and SCC cases compared with controls among 191 patients with high-risk HPV. The 67 cases with HPV types 16 and/or 18 had higher frequency of the GSTT1 null genotype than 186 with other types of HPV. There was no statistical difference in the polymorphic frequency of GSTM1 and p53 codon 72 genotypes between SILs and controls with or without high-risk HPV. These results suggest that GSTT1 null genotype may increase the risk of cervical cancer particularly in the cases with high-risk HPV types in a Japanese population. 相似文献
34.
Kazuki Oka Naotoshi Yoshiyama Koji Tojo Ryuichiro Machida Masatsugu Hatakeyama 《Development genes and evolution》2010,220(1-2):53-59
Larvae of the sawfly, Athalia rosae, have remarkable abdominal prolegs. We analyzed the morphogenesis of appendages and the expression of decapentaplegic and Distal-less genes during embryonic development to characterize the origin of prolegs. Proleg primordia in abdominal segments A1–A9 appeared shortly after the inner lobes (endites) of gnathal appendages were formed. These were located on the ventral plates, medioventral to the appendages of the other segments in light of serial homology. Nothing was seen where the main axis of the appendage should develop in abdominal segments. The primordia in A1 and A9 disappeared before larval hatching. Anal prolegs appeared separate from cerci, the main axes of appendages, which were formed temporarily in A11. The expression of decapentaplegic, which reflects the primary determination of appendages, was detected in the lateral juxtaposition with the prolegs. Distal-less was expressed in the main axes of appendages, protruding endites and the cerci, but not in prolegs and anal prolegs or the gnathal endites which do not protrude. These findings suggest a possibility that the abdominal and anal prolegs of A. rosae are outgrowths of ventral plates which derived from coxopodal elements, but not main axes of appendages. 相似文献
35.
Fujita M Asanuma H Hirata A Wakeno M Takahama H Sasaki H Kim J Takashima S Tsukamoto O Minamino T Shinozaki Y Tomoike H Hori M Kitakaze M 《American journal of physiology. Heart and circulatory physiology》2007,292(4):H2004-H2008
We have previously reported that the prolonged transient acidosis during early reperfusion mediates the cardioprotective effects in canine hearts. Recently, postconditioning has been shown to be one of the novel strategies to mediate cardioprotection. We tested the contribution of the prolonged transient acidosis to the cardioprotection of postconditioning. Open-chest anesthetized dogs subjected to 90-min occlusion of the left anterior descending coronary artery and 6-h reperfusion were divided into four groups: 1) control group; no intervention after reperfusion (n = 6); 2) postconditioning (Postcon) group; four cycles of 1-min reperfusion and 1-min reocclusion (n = 7); 3) Postcon + sodium bicarbonate (NaHCO(3)) group; four cycles of 1-min reperfusion and 1-min reocclusion with the administration of NaHCO(3) (n = 8); and 4) NaHCO(3) group; administration of NaHCO(3) without postconditioning (n = 6). Infarct size, the area at risk (AAR), collateral blood flow during ischemia, and pH in coronary venous blood were measured. The phosphorylation of Akt and extracellular signal-regulated kinase (ERK) in ischemic myocardium was assessed by Western blot analysis. Systemic hemodynamic parameters, AAR, and collateral blood flow were not different among the four groups. Postconditioning induced prolonged transient acidosis during the early reperfusion phase. Administration of NaHCO(3) completely abolished the infarct size-limiting effects of postconditioning. Furthermore, the phosphorylation of Akt and ERK in ischemic myocardium induced by postconditioning was also blunted by the cotreatment of NaHCO(3). In conclusion, postconditioning mediates its cardioprotective effects possibly via prolonged transient acidosis during the early reperfusion phase with the activation of Akt and ERK. 相似文献
36.
Takahashi R Kuramochi T Aoyagi K Hashimoto S Miyoshi I Kasai N Hakamata Y Kobayashi E Ueda M 《Transgenic research》2007,16(1):115-120
Cell marking is a very important procedure for identifying donor cells after cell and/or organ transplantation in vivo. Transgenic
animals expressing marker proteins such as enhanced green fluorescent protein (EGFP) in their tissues are a powerful tool
for research in fields of tissue engineering and regenerative medicine. The purpose of this study was to establish transgenic
rabbit lines that ubiquitously express EGFP under the control of the cytomegalovirus immediate early enhancer/beta-actin promoter
(CAG) to provide a fluorescent transgenic animal as a bioresource. We microinjected the EGFP expression vector into 945 rabbit
eggs and 4 independent transgenic candidate pups were obtained. Two of them died before sexual maturation and one was infertile.
One transgenic male candidate founder rabbit was obtained and could be bred by artificial insemination. The rabbit transmitted
the transgene in a Mendelian manner. Using fluorescence in situ hybridization analysis, we detected the transgene at 7q11
on chromosome 7 as a large centromeric region in two F1 offspring (one female and one male). Eventually, one transgenic line
was established. Ubiquitous EGFP florescence was confirmed in all examined organs. There were no gender-related differences
in fluorescence. The established CAG/EGFP transgenic rabbit will be an important bioresource and a useful tool for various
studies in tissue engineering and regenerative medicine. 相似文献
37.
Okada Y Ueshin Y Isotani A Saito-Fujita T Nakashima H Kimura K Mizoguchi A Oh-Hora M Mori Y Ogata M Oshima RG Okabe M Ikawa M 《Nature biotechnology》2007,25(2):233-237
Placental dysfunction underlies many complications during pregnancy, and better understanding of gene function during placentation could have considerable clinical relevance. However, the lack of a facile method for placenta-specific gene manipulation has hampered investigation of placental organogenesis and the treatment of placental dysfunction. We showed previously that transduction of fertilized mouse eggs with lentiviral vectors leads to transgene expression in both the fetus and the placenta. Here we report placenta-specific gene incorporation by lentiviral transduction of mouse blastocysts after removal of the zona pellucida. All of the placentas analyzed, but none of the fetuses, were transgenic. Application of this method substantially rescued mice deficient in Ets2, Mapk14 (also known as p38alpha) and Mapk1 (also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation. 相似文献
38.
Toyota M Matsuda K Kakutani T Terao Morita M Tasaka M 《The Plant journal : for cell and molecular biology》2011,65(4):589-599
Parental genomes are generally rearranged by two processes during meiosis: one is the segregation of homologous chromosomes and the other is crossing over between such chromosomes. Although the mechanisms underlying chromosome segregation and crossing over are well understood because of numerous genetic and molecular investigations, their contributions to the rearrangement of genetic information have not yet been analysed at a genome-wide level in Arabidopsis thaliana. We established 343 CAPS or SSLP markers to identify polymorphisms between two different Arabidopsis ecotypes, Col and Ler, which are distributed at an average distance of approximately 400kb between pairs of markers throughout the entire genome. Using these markers, crossover frequencies and chromosome segregation were quantified with respect to sex and age. Our large-scale analysis demonstrated that: (i) crossover frequencies during pollen formation were 1.79 and 1.37 times higher than those during megaspore formation in early and late flowers, respectively (P<0.001); (ii) the crossover frequencies during pollen formation were not significantly different between early and late flowers of main shoots (P>0.05), whereas the frequencies increased 1.30 times with shoot age during megaspore formation (P<0.001); (iii) the effect of aging depended on the developmental age of the individual shoot rather than on the age of the whole plant; and (iv) five chromosomes were randomly selected and mixed during meiosis. 相似文献
39.
Yumiko Ishikawa Kazuyuki Kobayashi Masatsugu Yamamoto Kyosuke Nakata Tetsuya Takagawa Yasuhiro Funada Yoshikazu Kotani Hajime Karasuyama Masaru Yoshida Yoshihiro Nishimura 《Respiratory research》2011,12(1):42
Background
There have been few reports on the role of Fc receptors (FcRs) and immunoglobulin G (IgG) in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs) in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa.Methods
In FcγRIIB deficient (KO) and C57BL/6 (WT) mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA). Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs) in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs) differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL).Results
In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously.Conclusion
Antigen-specific IgG ameliorates allergic airway inflammation via FcγRIIB on DCs. 相似文献40.
Shimmura C Suda S Tsuchiya KJ Hashimoto K Ohno K Matsuzaki H Iwata K Matsumoto K Wakuda T Kameno Y Suzuki K Tsujii M Nakamura K Takei N Mori N 《PloS one》2011,6(10):e25340