全文获取类型
收费全文 | 1710篇 |
免费 | 77篇 |
国内免费 | 22篇 |
专业分类
耳鼻咽喉 | 12篇 |
儿科学 | 27篇 |
妇产科学 | 50篇 |
基础医学 | 164篇 |
口腔科学 | 28篇 |
临床医学 | 101篇 |
内科学 | 349篇 |
皮肤病学 | 4篇 |
神经病学 | 122篇 |
特种医学 | 104篇 |
外科学 | 429篇 |
综合类 | 13篇 |
预防医学 | 21篇 |
眼科学 | 11篇 |
药学 | 104篇 |
肿瘤学 | 270篇 |
出版年
2024年 | 2篇 |
2023年 | 8篇 |
2022年 | 14篇 |
2021年 | 27篇 |
2020年 | 24篇 |
2019年 | 31篇 |
2018年 | 28篇 |
2017年 | 34篇 |
2016年 | 33篇 |
2015年 | 47篇 |
2014年 | 63篇 |
2013年 | 58篇 |
2012年 | 123篇 |
2011年 | 123篇 |
2010年 | 70篇 |
2009年 | 68篇 |
2008年 | 122篇 |
2007年 | 118篇 |
2006年 | 108篇 |
2005年 | 106篇 |
2004年 | 93篇 |
2003年 | 114篇 |
2002年 | 97篇 |
2001年 | 29篇 |
2000年 | 21篇 |
1999年 | 27篇 |
1998年 | 33篇 |
1997年 | 19篇 |
1996年 | 28篇 |
1995年 | 24篇 |
1994年 | 22篇 |
1993年 | 15篇 |
1992年 | 12篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1968年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有1809条查询结果,搜索用时 15 毫秒
21.
Dayton D. McMillan Junko Maeda Justin J. Bell Matthew D. Genet Garrett Phoonswadi Kelly A. Mann Susan L. Kraft Hisashi Kitamura Akira Fujimori Yukie Yoshii Takako Furukawa Yasuhisa Fujibayashi Takamitsu A. Kato 《Journal of radiation research》2015,56(5):784-791
Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a 64Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of 64Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from 64Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to 64Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D10 values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that 64Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from 64Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after 64Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that 64Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of 64Cu-ATSM as a cancer treatment modality for hypoxic tumors. 相似文献
22.
Absorption,distribution, metabolism and excretion of novel phosphodiesterase type 4 inhibitor ASP3258 in rats 下载免费PDF全文
Yoshiaki Ohtsu Takuya Sonoda Yoko Susaki Toshifumi Tohda Yasuhisa Fukunaga Takafumi Iwatsubo Kiyoshi Noguchi 《Biopharmaceutics & drug disposition》2015,36(1):34-48
The potent and selective phosphodiesterase 4 inhibitor ASP3258 is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease (COPD). After a single oral administration to rats, ASP3258 is rapidly absorbed with a bioavailability of 106%. In situ absorption data indicated that ASP3258 is mainly absorbed in the small intestine. Tissue distribution data after oral administration of 14C‐ASP3258 showed rapid and extensive distribution to various tissues. Excluding the gastrointestinal tract, the tissues with the highest concentrations were liver, heart and plasma. Liquid chromatography‐nuclear magnetic resonance spectroscopy data revealed that O‐glucuronidation of the carboxylic acid moiety of ASP3258 (formation of an acyl glucuronide) plays a key role in metabolism. No indication was found that the acyl glucuronide reacted with proteins in plasma or tissues. When 14C‐ASP3258 was orally administered to intact rats, urinary and fecal excretion accounted for 1.3% and 100.6% of the administered radioactivity, respectively. After a single oral administration of 14C‐ASP3258 to bile‐cannulated rats, urinary and biliary excretion accounted for 0.7% and 93.8% of the administered radioactivity, respectively. These findings suggest that fecal excretion via bile plays an important role in the elimination of ASP3258‐derived radioactivity. In vitro metabolic profiles were relatively similar among the species examined, suggesting that our findings in rats may help us to understand pharmacokinetics, efficacy and safety profiles in humans and other species. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
23.
Keisuke Kidoguchi Yasushi Kubota Shun Fujimoto Yasuhisa Sakata Haruna Kizuka-Sano Kyosuke Yamaguchi Hiroshi Ureshino Hiroo Katsuya Toshihiko Ando Motohiro Esaki Shinya Kimura 《Internal medicine (Tokyo, Japan)》2021,60(10):1601
Cronkhite-Canada syndrome (CCS) is a rare polyposis disorder accompanied by alopecia and onychodystrophy. A 63-year-old man with a history of CCS and repeated embolism developed progressive thrombocytopenia and mild anemia. Laboratory testing, a bone marrow examination, and magnetic resonance imaging of the spine resulted in a diagnosis of concurrent aplastic anemia (AA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were detected in a peripheral blood specimen. In addition, human leukocyte antigen (HLA) included DRB1*15:01 and DRB1*15:02. Mesalazine was discontinued in consideration of possible drug-induced pancytopenia. Immunosuppressive therapy ameliorated both the gastrointestinal symptoms of CCS and pancytopenia. A common autoimmune abnormality might underlie both CCS and AA. 相似文献
24.
Nakahara S Arimura Y Saito K Goto A Motoya S Shinomura Y Miyamoto A Imai K 《Diseases of the colon and rectum》2008,51(5):598-603
Purpose We investigated the association between steroid responsiveness and single nucleotide polymorphisms of SLC22A4/A5 located within inflammatory bowel disease 5 locus. Our goal is personalized steroid therapy adjusted to match individual
variations in drug responsiveness in each inflammatory bowel disease patient.
Methods Unrelated Japanese cohorts of 94 patients with Crohn’s, 94 patients with ulcerative colitis, and 257 healthy control subjects
were consecutively enrolled in this study. Genotyping and haplotype analysis focusing on steroid responsiveness was performed
by using 15 single nucleotide polymorphisms.
Results The G allele of −368T > G in SLC22A5, in which strong linkage disequilibrium was observed and the limited diversity of three haplotypes was estimated, was significantly
associated with steroid resistance in Japanese patients with Crohn’s disease (P = 0.016). Haplotype analysis between −446C > T and −368T > G in the SLC22A5 promoter region showed that the CG allele appeared to be a risk haplotype for steroid resistance (CG: odds ratio, 4.13; 95
percent confidence interval, 1.41–12.1; P = 0.016).
Conclusions This extensive linkage disequilibrium may form a general risk haplotype for steroid resistance in Crohn’s disease in Japanese.
Further analyses of the pharmacogenomics of steroid responsiveness are warranted to achieve the goal of individualized steroid
therapy against inflammatory bowel disease.
Supported by a grant-in-aid from the Ministry of Health, Labour and Welfare (K.I.), Japan.
Address of correspondence: Yoshiaki Arimura, M.D., First Department of Internal Medicine, Sapporo Medical University, S-1,
W-16, Chuo-ku, Sapporo, 060-8543, Japan. E-mail: arimura@sapmed.ac.jp 相似文献
25.
K Nagao Y Higashimoto Y Shinomura S Himeno Y Miyazaki Y Yasunaga S Tarui 《The American journal of gastroenterology》1990,85(11):1489-1492
We studied the temporal profile of urinary NH2-terminal big gastrin immunoreactivity (NT G-34-IR) excretion in order to evaluate the dynamics of gastrin secretion. The temporal profile of urinary NT G-34-IR excretion in normal subjects represented three peaks corresponding to each meal. In contrast, the profile in antrectomized patients and patients under total parenteral nutrition (TPN) represented a flat pattern. Urinary NT G-34-IR excretions during fasting 2-h periods in antrectomized patients and TPN patients were about one-sixth and one-third, respectively, of basal NT G-34-IR excretion in normal subjects (53.1 +/- 13.9 pmol/h). Total urinary NT G-34-IR excretion during 24 h both in antrectomized patients (220 +/- 35 pmol/24 h) and TPN patients (390 +/- 68 pmol/24 h) was also significantly lower than in normal subjects (1985 +/- 403 pmol/24 h). The present study showed that the main source of urinary NT G-34-IR is the gastric antrum, that the main factor fluctuating its excretion is food intake, and that long-term TPN reduces basal gastrin secretion. Urinary NT G-34-IR would be a useful indicator for total gastrin secretion. 相似文献
26.
The relationship between gallbladder disease and smoking and drinking habits in middle-aged Japanese 总被引:1,自引:0,他引:1
Okamoto M Yamagata Z Takeda Y Yoda Y Kobayashi K Fujino MA 《Journal of gastroenterology》2002,37(6):455-462
Background:
Background: Few studies have investigated the association between smoking and ultrasonographically diagnosed gallbladder (GB) disease,
and their results were uncertain. This study was conducted to examine the association between smoking and drinking and GB
diseases.
Methods: A total of 9947 subjects (age, 30–69 years; 4953 men and 4994 women) voluntarily received a paid medical check-up at our
center in Yamanashi Prefecture in Japan. All of the subjects underwent abdominal ultrasonographic (US) examination, a demographic
check, and a biochemical test, and answered a self-administered questionnaire asking about smoking habits and alcohol consumption.
Of the 9947 subjects, 483 had gallstones, 819 had gallbladder polyps, and 169 were in a state of postcholecystectomy. We compared
the findings in this group with the findings in 8417 people (4144 males and 4273 females) with normal gallbladder.
Results: Multiple regression analysis among males showed that cigarette smoking was inversely related to GB polyps (odds ratio, [OR],
0.76; 95% confidence internal [CI], 0.59–0.98 and OR, 0.74; 95% CI, 0.56–0.98, respectively, for current and ex-smokers).
Ex-smokers a showed positive association with the postcholecystectomy state (OR, 2.56; 95% CI, 1.18–5.52). Light drinkers
showed an inverse relation to GB stones (OR, 0.69; 95% CI, 0.49–0.99), and heavy drinkers showed an inverse relation to GB
polyps (OR, 0.68; 95% CI, 0.51–0.90). Current drinkers showed an inverse relation to the postcholecystectomy state (OR, 0.48;
95% CI, 0.28–0.83).
Conclusions: Cigarette smoking was inversely related to gallbladder polyps in males and was positively related to the postcholecystectomy
state. Drinking was inversely related to gallstones, GB polyps, and the postcholecystectomy state in males.
Received: July 19, 2001 / Accepted: November 2, 2001 相似文献
27.
Sakata Y Iwakiri R Amemori S Yamaguchi K Fujise T Otani H Shimoda R Tsunada S Sakata H Ikeda Y Ando T Nakafusa Y Fujimoto K 《European journal of gastroenterology & hepatology》2008,20(7):629-633
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurring inflammation of the colorectal mucosa. Recently, cytapheresis has emerged as a new treatment for patients with UC. Removal methods are mainly performed with beads [granulocyte and monocyte/macrophage adsorptive apheresis (GMCAP)] or filters [leukocytapheresis (LCAP)]. Both treatments have been reported to be effective for active UC. There have been few trials, however, comparing the efficacy of GMCAP and LCAP. In this study, we prospectively evaluated the efficacy of LCAP and GMCAP for the treatment of active UC. METHODS: Thirty-nine patients [18 male, 21 female; mean age 38.7 years; duration of disease 6 years; clinical activity index (CAI) >6 points] with moderate-to-severe active UC were randomly assigned to the LCAP (n=21) or GMCAP group (n=17). Adacolumn (cellulose acetate beads; Japan Immunoresearch Laboratories, Takasaki, Japan) for GMCAP and Cellsorba EX (polyethylene phthalate fibers; Asahi Medical Co. Ltd, Tokyo, Japan) for LCAP were used for leukocyte removal. Patients received two sessions of cytapheresis in the first week, followed by four weekly administrations. Steroid doses were tapered if patients achieved clinical improvement. When the CAI score had decreased by 5 points or more, the patient was considered to have improved. RESULTS: Thirteen patients in the GMCAP group and 14 in the LCAP group achieved clinical improvement. No significant difference was found in clinical response and clinical course between LCAP and GMCAP. Hemoglobin levels were significantly decreased immediately after one session of cytapheresis in the LCAP group. No severe adverse effects were observed in any of the patients. No significant differences were observed in any clinical parameters predictive of a response to either LCAP or GMCAP. But in all patients receiving cytapheresis, a high CAI score was a significant risk factor for treatment failure. All of the cytapheresis nonresponders had CAI scores >or=16. CONCLUSION: Both GMCAP and LCAP were effective treatments for active UC. Patients with severe UC and a high CAI score were, however, refractory to treatment. 相似文献
28.
Increased group II phospholipase A2 in colonic mucosa of patients with Crohn's disease and ulcerative colitis. 总被引:3,自引:1,他引:3 下载免费PDF全文
The immunochemical protein content of group II phospholipase A2 (PLA2) and PLA2 enzymatic activity were measured for colonic mucosal biopsy samples obtained from patients with either Crohn's disease of the colon or ulcerative colitis, and control patients without inflammatory bowel disease. Immunoreactive group II PLA2 (IR-PLA2 II) content and PLA2 activity in actively inflamed colonic mucosa of Crohn's disease patients were significantly higher than those in inactively inflamed mucosa of Crohn's disease patients and the colonic mucosa of controls. IR-PLA2 II content and PLA2 activity in severely inflamed mucosa of ulcerative colitis patients were significantly higher than those in the colonic mucosa of the controls. Mucosal PLA2 enzymatic activity was closely correlated with mucosal IR-PLA2 II content in patients with Crohn's disease and ulcerative colitis. These results suggest that an increase in PLA2 enzymatic activity in inflamed colonic mucosa of Crohn's disease and ulcerative colitis was mainly attributed to increased protein content of group II PLA2, and that an increase in mucosal group II PLA2 may be involved in the pathogenesis of intestinal inflammation of Crohn's disease and ulcerative colitis. 相似文献
29.
30.