全文获取类型
收费全文 | 216篇 |
免费 | 13篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 1篇 |
基础医学 | 40篇 |
口腔科学 | 1篇 |
临床医学 | 19篇 |
内科学 | 66篇 |
皮肤病学 | 1篇 |
神经病学 | 13篇 |
特种医学 | 4篇 |
外科学 | 20篇 |
预防医学 | 20篇 |
药学 | 19篇 |
肿瘤学 | 25篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 8篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 8篇 |
2013年 | 11篇 |
2012年 | 8篇 |
2011年 | 16篇 |
2010年 | 5篇 |
2009年 | 13篇 |
2008年 | 16篇 |
2007年 | 14篇 |
2006年 | 13篇 |
2005年 | 7篇 |
2004年 | 8篇 |
2003年 | 14篇 |
2002年 | 7篇 |
2001年 | 3篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 9篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有230条查询结果,搜索用时 15 毫秒
101.
Satoshi Yokoyama Satoshi Tamaru Shinya Tamaki Daisuke Nakanishi Akiya Mori Tomokazu Yamakawa Takaaki Ao Yasuhiko Sakata Toshiro Mizuno Takuya Iwamoto Kenichi Watanabe Makoto Simomura Keiki Kawakami Naomi Konishi Shinichi Kageyama Shoichiro Ohtani Tomomi Yamada Susumu Ban Kazuya Ooi 《Clinical breast cancer》2018,18(2):e157-e165
Introduction
Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV.Patients and Methods
We evaluated CINV attributable to anthracycline-based chemotherapy in Japanese breast cancer patients treated with an antiemetic regimen that included palonosetron, aprepitant, and dexamethasone. Furthermore, we investigated the associations between CINV and single nucleotide polymorphisms in 6 candidate genes.Results
Emesis episodes were rarely observed in the 125 patients included in the present survey (7.2%; n = 9); however, significant nausea occurred in more than one half of the patients (52.8%; n = 66). In particular, acute significant nausea was not effectively controlled. Multivariate logistic regression analysis revealed that the ABCG2 (rs2231142) AA genotype is significantly associated with acute significant nausea (odds ratio, 4.87; 95% confidence interval, 1.01-23.60; P = .049).Conclusion
The findings of the present study provide significant insights for developing personalized antiemetic strategies for breast cancer patients receiving anthracycline-based chemotherapy. 相似文献102.
Keiki Ogino Kenjiro Nagaoka Tomoaki Okuda Akira Oka Masayuki Kubo Eri Eguchi Yoshihisa Fujikura 《Environmental toxicology》2017,32(3):1047-1054
The allergic inflammatory effects of particulate matter (PM) 2.5, collected with the cyclone system in Yokohama city in Japan, were investigated in NC/Nga mice, which are hypersensitive to mite allergens. PM2.5 with alum was injected intraperitoneally for sensitization. Five days later, 200 μg of PM2.5 in 25 μL of saline was administered to mice intranasally five times for further sensitization. On the 11th day, PM2.5 was administered as a challenge. On the 12th day, mice were examined for airway hyperresponsiveness (AHR), the bronchoalveolar lavage fluid (BALF) cell count, mRNA expression of Th1, Th2 cytokines, and metallothioneins in lung tissue, and histopathology. PM2.5 increased AHR, total cell numbers including eosinophils in BALF, and mRNA levels of IL‐5, IL‐22, eotaxin, eotaxin 2, and metallothionein 3. In PM2.5‐induced lungs, inflammation was observed around the bronchus. These results demonstrate that PM2.5 alone, collected with the cyclone system in Yokohama city in Japan, induces asthma‐like airway inflammation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1047–1054, 2017. 相似文献
103.
Noriyoshi Ogino Koichiro Miyagawa Kenjiro Nagaoka Yuki Matsuura-Harada Shihona Ogino Masashi Kusanaga Shinji Oe Yuichi Honma Masaru Harada Masamitsu Eitoku Narufumi Suganuma Keiki Ogino 《Nutrients》2021,13(3)
Increased circulating levels of free fatty acids, especially saturated ones, are involved in disease progression in the non-alcoholic fatty liver. Although the mechanism of saturated fatty acid-induced toxicity in the liver is not fully understood, oxidative stress may be deeply involved. We examined the effect of increased palmitic acid, the most common saturated fatty acid in the blood, on the liver of BALB/c mice via tail vein injection with palmitate. After 24 h, among several anti-oxidative stress response genes, only heme oxygenase-1 (HO-1) was significantly upregulated in palmitate-injected mice compared with that in vehicle-injected mice. Elevation of HO-1 mRNA was also observed in the fatty liver of high-fat-diet-fed mice. To further investigate the role of HO-1 on palmitic acid-induced oxidative stress, in vitro experiments were performed to expose palmitate to HepG2 cells. SiRNA-mediated knockdown of HO-1 significantly increased the oxidative stress induced by palmitate, whereas pre-treatment with SnCl2, a well-known HO-1 inducer, significantly decreased it. Moreover, SB203580, a selective p38 inhibitor, reduced HO-1 mRNA expression and increased palmitate-induced oxidative stress in HepG2 cells. These results suggest that the HO-1-mediated anti-oxidative stress compensatory reaction plays an essential role against saturated fatty acid-induced lipotoxicity in the liver. 相似文献
104.
105.
Inflammatory airway responses by nasal inoculation of suspended particulate matter in NC/Nga mice
下载免费PDF全文
![点击此处可从《Environmental toxicology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Keiki Ogino Noriko Takahashi Masayuki Kubo Akihito Takeuchi Motoharu Nakagiri Yoshihisa Fujikura 《Environmental toxicology》2014,29(6):642-654
To evaluate the allergic effect of airborne particulate matter (PM) on the airway, separated soluble supernatant (Sup) and insoluble precipitate (Pre) in suspended PM were inoculated into NC/Nga mice with a high sensitivity for mite allergens. Sup, Pre, or both Sup and Pre with or without pronase treatment were inoculated via the nasal route five times for sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 14th day, mice were examined for airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, mRNA expression of Th1 and Th2 cytokines in the lung tissue, and histopathology. Synergistic effects of Sup and Pre were observed as increases in AHR and a histopathological change of Periodic acid‐Schiff (PAS) staining. Increases in neutrophils, macrophages, and lymphocytes of BALF cells were dependent on Pre. The expression of IL‐4 mRNA was increased by Sup, and those of IL‐5 mRNA and Il‐13 mRNA was increased by Sup and Pre. Augmented AHR, mRNA expression of IL‐4, peribronchial inflammation, and PAS staining by Sup plus Pre were attenuated by treatment of Sup with pronase to digest proteins. These results suggest that some proteins of ambient PM may be important environmental factors for AHR and airway inflammation with the aid of insoluble particulates, although some soluble factors such as endotoxins cannot be ruled out. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 642–654, 2014. 相似文献
106.
107.
Nagaharu K Zhang X Yoshida T Katoh D Hanamura N Kozuka Y Ogawa T Shiraishi T Imanaka-Yoshida K 《The American journal of pathology》2011,178(2):754-763
Tenascin C (TNC) is an extracellular matrix glycoprotein up-regulated in solid tumors. Higher TNC expression is shown in invading fronts of breast cancer, which correlates with poorer patient outcome. We examined whether TNC induces epithelial-mesenchymal transition (EMT) in breast cancer. Immunohistochemical analysis of invasive ductal carcinomas showed that TNC deposition was frequent in stroma with scattered cancer cells in peripheral margins of tumors. The addition of TNC to the medium of the MCF-7 breast cancer cells caused EMT-like change and delocalization of E-cadherin and β-catenin from cell-cell contact. Although amounts of E-cadherin and β-catenin were not changed after EMT in total lysates, they were increased in the Triton X-100-soluble fractions, indicating movement from the membrane into the cytosol. In wound healing assay, cells were scattered from wound edges and showed faster migration after TNC treatment. The EMT phenotype was correlated with SRC activation through phosphorylation at Y418 and phosphorylation of focal adhesion kinase (FAK) at Y861 and Y925 of SRC substrate sites. These phosphorylated proteins colocalized with αv integrin-positive adhesion plaques. A neutralizing antibody against αv or a SRC kinase inhibitor blocked EMT. TNC could induce EMT-like change showing loss of intercellular adhesion and enhanced migration in breast cancer cells, associated with FAK phosphorylation by SRC; this may be responsible for the observed promotion of TNC in breast cancer invasion. 相似文献
108.
Notch2 signaling is required for proper mast cell distribution and mucosal immunity in the intestine
Sakata-Yanagimoto M Sakai T Miyake Y Saito TI Maruyama H Morishita Y Nakagami-Yamaguchi E Kumano K Yagita H Fukayama M Ogawa S Kurokawa M Yasutomo K Chiba S 《Blood》2011,117(1):128-134
Notch receptor-mediated signaling is involved in the developmental process and functional modulation of lymphocytes, as well as in mast cell differentiation. Here, we investigated whether Notch signaling is required for antipathogen host defense regulated by mast cells. Mast cells were rarely found in the small intestine of wild-type C57BL/6 mice but accumulated abnormally in the lamina propria of the small-intestinal mucosa of the Notch2-conditional knockout mice in naive status. When transplanted into mast cell-deficient W(sh)/W(sh) mice, Notch2-null bone marrow-derived mast cells were rarely found within the epithelial layer but abnormally localized to the lamina propria, whereas control bone marrow-derived mast cells were mainly found within the epithelial layer. After the infection of Notch2 knockout and control mice with L3 larvae of Strongyloides venezuelensis, the abundant number of mast cells was rapidly mobilized to the epithelial layer in the control mice. In contrast, mast cells were massively accumulated in the lamina propria of the small intestinal mucosa in Notch2-conditional knockout mice, accompanied by impaired eradication of Strongyloides venezuelensis. These findings indicate that cell-autonomous Notch2 signaling in mast cells is required for proper localization of intestinal mast cells and further imply a critical role of Notch signaling in the host-pathogen interface in the small intestine. 相似文献
109.
110.
A Ti-Nb-Sn alloy was developed as a new β-type titanium alloy which had a low Young's modulus and high strength. The Young's modulus of the Ti-Nb-Sn alloy was reduced to about 45 GPa by cold rolling, much closer to human cortical bone (10-30 GPa) than that of Ti-6Al-4V alloy (110 GPa) and other β-type titanium alloys developed for biomedical applications. The tensile strength of the Ti-Nb-Sn alloy was increased to a level greater than that of Ti-6Al-4V alloy by heat treatment after severe cold rolling. In this study the cytotoxicity of Ti-25Nb-11Sn alloy was evaluated in direct contact cell culture tests using metal disks and the bone tissue compatibility - examined using metal rods inserted into the medullary canal of rabbit femurs. The remarkable findings were that: (1) there were no significant differences in the relative growth ratio and relative absorbance ratio between cells grown with the Ti-Nb-Sn alloy, Ti-6Al-4V alloy and CP-Ti in direct contact cell culture tests; (2) there were no significant differences in the load at failure between the Ti-Nb-Sn alloy and Ti-6Al-4V alloy in pull-out metal rods tests; (3) there were no significant differences in new bone formation around metal rods between the Ti-Nb-Sn alloy and Ti-6Al-4V alloy in histological evaluations. The new Ti-Nb-Sn alloy with an elasticity closer to that of human bone is thus considered to be bioinert while also having a high degree of bone compatibility similar to that of Ti-6Al-4V alloy. 相似文献