全文获取类型
收费全文 | 476篇 |
免费 | 32篇 |
专业分类
508篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 9篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 15篇 |
2014年 | 26篇 |
2013年 | 29篇 |
2012年 | 29篇 |
2011年 | 40篇 |
2010年 | 12篇 |
2009年 | 16篇 |
2008年 | 39篇 |
2007年 | 36篇 |
2006年 | 31篇 |
2005年 | 31篇 |
2004年 | 30篇 |
2003年 | 30篇 |
2002年 | 32篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 8篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 8篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 8篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1967年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有508条查询结果,搜索用时 15 毫秒
31.
Hidekazu Tanaka Takahiro Yamaguchi Kae Hachiya Shingo Kamei Satoshi Ishihara Masahide Hayashi Shinichi Ogawa Hironori Nishibori Satoshi Goshima Masayuki Matsuo 《Reports of Practical Oncology and Radiotherapy》2018,23(1):28-33
Aim
This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.Background
A total of 1091 patients with localized prostate cancer were recruited between March 2006 and July 2014. The patients were stratified into low- (n = 205 [18.8%]), intermediate- (n = 450 [41.2%]), high- (n = 345 [31.6%]), and very high-risk (n = 91 [8.3%]) groups according to the National Comprehensive Cancer Network classification. All patients were irradiated via IMRT at a dose of 74–78 Gy with or without androgen-deprivation therapy. The mean follow-up period was 50 months (range, 2–120 months).Results
The biochemical failure-free rate (BFFR), the clinical failure-free rate, and the overall survival rate at the 5-year follow-up for all patients was 91.3%, 96.2%, and 99.1%, respectively. In univariate analysis, the prostate-specific antigen (PSA) levels (≤20 vs. >20 ng/ml) were significantly correlated with BFFR. A trend toward higher BFFR was noted in patients with a Gleason score (GS) of ≤7 than in patients with GS ≥8. In multivariate analysis, only PSA (≤20 vs. >20 ng/ml) was significantly correlated with BFFR. The cumulative incidence rate of gastrointestinal and genitourinary toxicity (≥grade 2) at the 5-year follow-up was 11.4% and 4.3%, respectively.Conclusions
The findings of this study indicate that IMRT is well tolerated and is associated with both good long-term tumor control and excellent outcomes in patients with localized prostate cancer. 相似文献32.
33.
34.
35.
36.
Gendron C Kashiwagi M Lim NH Enghild JJ Thøgersen IB Hughes C Caterson B Nagase H 《The Journal of biological chemistry》2007,282(25):18294-18306
Aggrecanases have been characterized as proteinases that cleave the Glu373-Ala374 bond of the aggrecan core protein, and they are multidomain metalloproteinases belonging to the ADAMTS (adamalysin with thrombospondin type 1 motifs) family. The first aggrecanases discovered were ADAMTS-4 (aggrecanase 1) and ADAMTS-5 (aggrecanase 2). They contain a zinc catalytic domain followed by non-catalytic ancillary domains, including a disintegrin domain, a thrombospondin domain, a cysteine-rich domain, and a spacer domain. In the case of ADAMTS-5, a second thrombospondin domain follows the spacer domain. We previously reported that the non-catalytic domains of ADAMTS-4 influence both its extracellular matrix interaction and proteolytic abilities. Here we report the effects of these domains of ADAMTS-5 on the extracellular matrix interaction and proteolytic activities and compare them with those of ADAMTS-4. Although the spacer domain was critical for ADAMTS-4 localization in the matrix, the cysteine-rich domain influenced ADAMTS-5 localization. Similar to previous reports of other ADAMTS family members, very little proteolytic activity was detected with the ADAMTS-5 catalytic domain alone. The sequential inclusion of each carboxyl-terminal domain enhanced its activity against aggrecan, carboxymethylated transferrin, fibromodulin, decorin, biglycan, and fibronectin. Both ADAMTS-4 and -5 had a broad optimal activity at pH 7.0-9.5. Aggrecanolytic activities were sensitive to the NaCl concentration, but activities on non-aggrecan substrates, e.g. carboxymethylated transferrin, were not affected. Although ADAMTS-4 and ADAMTS-5 had similar general proteolytic activities, the aggrecanase activity of ADAMTS-5 was at least 1,000-fold greater than that of ADAMTS-4 under physiological conditions. Our studies suggest that ADAMTS-5 is a major aggrecanase in cartilage metabolism and pathology. 相似文献
37.
Kaneko S Okuda-Ashitaka E Ando A Nishimura K Igarashi K Maeda M Furuta K Suzuki M Matsumura M Ito S 《American journal of physiology. Cell physiology》2007,293(2):C729-C737
We previously showed that ornithine was mainly transported via cationic amino acid transporter (CAT)-1 in human retinal pigment epithelial (RPE) cell line, human telomerase RT (hTERT)-RPE, and that CAT-1 was involved in ornithine cytotoxicity in ornithine--aminotransferase (OAT)-deficient cell produced by a OAT specific inhibitor, 5-fluoromethylornithine (5-FMO). We showed here that CAT-1 mRNA expression was increased by ornithne in OAT-deficient RPE cells, which was reversed by an inhibitor of ornithine decarboxylase (ODC), -difluoromethylornithine (DFMO). Polyamines, especially spermine, one of the metabolites of ODC, also enhanced the expression of CAT-1 mRNA. ODC mRNA expression was also increased by ornithine and polyamines, and gene silencing of ODC by siRNA decreased ornithine transport activity and its cytotoxicity. In addition, the mRNA of nuclear protein c-myc was also increased in 5-FMO- and ornithine-treated hTERT-RPE cells, and gene silencing of c-myc prevented the induction of CAT-1 and ODC. Increases in expression of CAT-1, ODC, and c-myc, and the inhibition of these stimulated expression by DFMO were also observed in primary porcine RPE cells. These results suggest that spermine plays an important role in stimulation of mRNA expression of CAT-1, which is a crucial role in ornithine cytotoxicity in OAT-deficient hTERT-RPE cells. ornithine transport; ornithine decarboxylase; c-myc 相似文献
38.
Nishizaki C Nishikawa M Yata T Yamada T Takahashi Y Oku M Yurimoto H Sakai Y Nakanishi K Takakura Y 《Free radical biology & medicine》2011,51(3):773-779
Surgical trauma, which is inevitably associated with the surgical removal of cancer, has been reported to accelerate tumor metastasis. The close association of reactive oxygen species with the trauma and tumor metastasis supports the possibility of using antioxidants for the inhibition of metastasis. To inhibit surgical trauma-enhanced peritoneal dissemination, human catalase (hCAT) derivatives, i.e., hCAT-nona-arginine peptide (hCAT-R9) and hCAT-albumin-binding peptide (hCAT-ABP), were designed to increase the retention time of the antioxidant enzyme in the abdominal cavity after intraperitoneal administration. Both 125I-labeled derivatives showed significantly prolonged retention in the cavity compared to 125I-hCAT. Cauterization of the cecum of mice with a hot iron, an experimental model of surgical trauma, induced abdominal adhesions. In addition, cauterization followed by colon26 tumor cell inoculation increased lipid peroxidation in the cecum and mRNA expression of molecules associated with tissue repair/adhesion and inflammation in the peritoneum. hCAT derivatives significantly suppressed the increased mRNA expression. The cauterization also increased the number of tumor cells in the abdominal organs, and the number was significantly reduced by hCAT-R9 or hCAT-ABP. These results indicate that hCAT-R9 and hCAT-ABP, both of which have a long retention time in the peritoneal cavity, can be effective at inhibiting surgery-induced peritoneal metastasis. 相似文献
39.
Kawaguchi S Kurihara H King R Hale L Berli T Robinson JP Ishida A Wakita M Virtue P Nicol S Ishimatsu A 《Biology letters》2011,7(2):288-291
Antarctic krill embryos and larvae were experimentally exposed to 380 (control), 1000 and 2000 µatm pCO2 in order to assess the possible impact of ocean acidification on early development of krill. No significant effects were detected on embryonic development or larval behaviour at 1000 µatm pCO2; however, at 2000 µatm pCO2 development was disrupted before gastrulation in 90 per cent of embryos, and no larvae hatched successfully. Our model projections demonstrated that Southern Ocean sea water pCO2 could rise up to 1400 µatm in krill''s depth range under the IPCC IS92a scenario by the year 2100 (atmospheric pCO2 788 µatm). These results point out the urgent need for understanding the pCO2-response relationship for krill developmental and later stages, in order to predict the possible fate of this key species in the Southern Ocean. 相似文献
40.
Ueno M Itoh M Kong L Sugihara K Asano M Takakura N 《Molecular and cellular biology》2005,25(23):10528-10532
Psf1 (partner of sld five 1) forms a novel heterotetramer complex, GINS (Go, Ichi, Nii, and San; five, one, two, and three, respectively, in Japanese), with Sld5, Psf2, and Psf3. The formation of this complex is essential for the initiation of DNA replication in yeast and Xenopus laevis egg extracts. Although all of the components are well conserved in higher eukaryotes, the biological function in vivo is largely unknown. We originally cloned the mouse ortholog of PSF1 from a hematopoietic stem cell cDNA library and found that PSF1 is expressed in blastocysts, adult bone marrow, and testis, in which the stem cell system is active. Here we used the gene-targeting technique to determine the physiological function of PSF1 in vivo. Mice homozygous for a nonfunctional mutant of PSF1 died in utero around the time of implantation. PSF1-/- blastocysts failed to show outgrowth in culture and exhibited a cell proliferation defect. Our data clearly indicate that PSF1 is required for early embryogenesis. 相似文献