全文获取类型
收费全文 | 413篇 |
免费 | 21篇 |
专业分类
耳鼻咽喉 | 8篇 |
妇产科学 | 1篇 |
基础医学 | 38篇 |
临床医学 | 10篇 |
内科学 | 63篇 |
皮肤病学 | 142篇 |
神经病学 | 57篇 |
特种医学 | 5篇 |
外科学 | 61篇 |
预防医学 | 7篇 |
眼科学 | 3篇 |
药学 | 18篇 |
肿瘤学 | 21篇 |
出版年
2023年 | 5篇 |
2022年 | 1篇 |
2021年 | 6篇 |
2020年 | 7篇 |
2019年 | 11篇 |
2018年 | 9篇 |
2017年 | 19篇 |
2016年 | 15篇 |
2015年 | 20篇 |
2014年 | 16篇 |
2013年 | 15篇 |
2012年 | 19篇 |
2011年 | 17篇 |
2010年 | 9篇 |
2009年 | 16篇 |
2008年 | 12篇 |
2007年 | 20篇 |
2006年 | 29篇 |
2005年 | 27篇 |
2004年 | 21篇 |
2003年 | 28篇 |
2002年 | 34篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 6篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有434条查询结果,搜索用时 15 毫秒
81.
Transient improvement of urticaria induces poor adherence as assessed by Morisky Medication Adherence Scale‐8 下载免费PDF全文
Sakae Kaneko Koji Masuda Takaaki Hiragun Naoko Inomata Masutaka Furue Daisuke Onozuka Satoshi Takeuchi Hiroyuki Murota Makoto Sugaya Hidehisa Saeki Yoichi Shintani Yuichiro Tsunemi Shinya Abe Miwa Kobayashi Yuki Kitami Miki Tanioka Shinichi Imafuku Masatoshi Abe Akihito Hagihara Donald E. Morisky Norito Katoh 《The Journal of dermatology》2015,42(11):1078-1082
Poor adherence to medication is a major public health challenge. Here, we aimed to determine the adherence to oral and topical medications and to analyze underlying associated factors using the translated Japanese version of Morisky Medication Adherence Scale‐8 regarding urticaria treatment. Web‐based questionnaires were performed for 3096 registered dermatological patients, along with a subanalysis of 751 registered urticaria patients in this study. The adherence to oral medication was significantly associated with the frequency of hospital visits. Variables that affected the adherence to topical medication included age and experience of drug effectiveness. The rate of responses that “It felt like the symptoms had improved” varied significantly among the dermatological diseases treated with oral medications. Dermatologists should be aware that adherence to the treatment of urticaria is quite low. Regular visits and active education for patients with urticaria are mandatory in order to achieve a good therapeutic outcome by increasing the adherence. 相似文献
82.
Chizuko Yano Hidehisa Saeki Mayumi Komine Shinji Kagami Yuichiro Tsunemi Mamitaro Ohtsuki Hidemi Nakagawa 《ANNALS OF DERMATOLOGY》2015,27(2):152-156
BackgroundCC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes.ObjectiveTo identify the mechanism underlying CCL22 production by HaCaT cells.MethodsWe investigated the signal transduction pathways by which TNF-α and IFN-γ stimulate HaCaT cells to produce CCL22 by adding various inhibitors.ResultsTNF-α- and IFN-γ-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1.ConclusionOur results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells. 相似文献
83.
84.
Alaa M Shibuya K Fujiwara T Wada H Hoshino H Yoshida S Suzuki M Hiroshima K Nakatani Y Mohamed-Hussein AA Elkholy MM Mahfouz T Yoshino I 《Lung cancer (Amsterdam, Netherlands)》2011,72(3):303-308
Objectives
To assess risk of lung cancer (LC) in patients with preinvasive bronchial lesions and to identify factors associated with higher risk.Methods
124 patients with one or more preinvasive bronchial lesions and normal chest computed tomography (CT) (mean age 66.7 years, 121 males and 3 females), followed-up by white light and autofluorescence bronchoscopy (AFB) every 4-6 mo and chest CT every 6-12 mo, end points were development of carcinoma in situ (CIS) or LC.Results
Among 124 patients with 240 preinvasive bronchial lesions, 20 CIS or LC lesions were detected during follow-up in 20 (16%) patients, 7 were detected as new endobronchial lesions, 10 as new peripheral lesions and 3 as local progression from severe dysplasia to CIS. Median time to progression from the same site or development of CIS/LC elsewhere was 24 months (range: 6-54 mo). The Cumulative risk of development of CIS/LC was 7% at one year, 20% at three years and 44% at 5 years. Among detected lung cancers, 80% were stage 0 or stage I and underwent treatment with curative intent. Diagnosis of new SD during follow-up (p = 0.0001), chronic obstructive pulmonary disease (COPD) (p = 0.001) or smoking index >52 pack-year (p = 0.042) was associated with higher risk. Even after controlling for other risk factors, COPD was associated with risk for lung cancer. Baseline lesion grade was not predictive of patient outcome (p = 0.146).Conclusion
Patients with preinvasive bronchial lesions, especially those with new SD during follow-up, COPD or smoking >52 pack-year are at high risk of LC, AFB and CT follow-up facilitated early detection and treatment with curative intent. 相似文献85.
Kawakita Y Banno H Ohashi T Tamura T Yusa T Nakayama A Miki H Iwata H Kamiguchi H Tanaka T Habuka N Sogabe S Ohta Y Ishikawa T 《Journal of medicinal chemistry》2012,55(8):3975-3991
To develop novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) kinase inhibitors, we explored pyrrolo[3,2-d]pyrimidine derivatives bearing bicyclic fused rings designed to fit the back pocket of the HER2/EGFR proteins. Among them, the 1,2-benzisothiazole (42m) ring was selected as a suitable back pocket binder because of its potent HER2/EGFR binding and cell growth inhibitory (GI) activities and pseudoirreversibility (PI) profile as well as good bioavailability (BA). Ultimately, we arrived at our preclinical candidate 51m by optimization of the N-5 side chain to improve CYP inhibition and metabolic stability profiles without a loss of potency (HER2/EGFR inhibitory activity, IC(50), 0.98/2.5 nM; and GI activity BT-474 cells, GI(50), 2.0 nM). Reflecting the strong in vitro activities, 51m exhibited potent tumor regressive efficacy against both HER2- and EGFR-overexpressing tumor (4-1ST and CAL27) xenograft models in mice at oral doses of 50 mg/kg and 100 mg/kg. 相似文献
86.
Makoto Suzuki MD Hironobu Wada MD Mitsuru Yoshino MD Lei Tian MD Hisayuki Shigematsu MD Hidemi Suzuki MD Mahmoud Alaa MD Hajime Tamura MD Taiki Fujiwara MD Kaoru Nagato MD Shinichiro Motohashi MD Yasumitsu Moriya MD Hidehisa Hoshino MD Shigetoshi Yoshida MD Kiyoshi Shibuya MD Kenzo Hiroshima MD Yukio Nakatani MD Ichiro Yoshino MD 《Annals of surgical oncology》2010,17(3):878-888
Background
The aim of this study was to evaluate the molecular influence of chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small cell lung cancer (NSCLC).Materials and Methods
The methylation profiles of 12 genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were determined for samples from 229 NSCLC patients. In addition, protein expression of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of COPD.Results
IL-12Rβ2 and Wif-1 methylation and HER2 overexpression were more frequent events in the COPD group. Eighty nonmalignant lung tissues had no correlation with any molecular changes between the COPD and the non-COPD group. EGFR mutation was significantly higher in the non-COPD group, while EGFR expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a negative prognostic factor, while methylation of p16INK4A and WNT antagonist genes was a negative prognostic factor in the non-COPD group.Conclusions
Novel characteristics of COPD-related NSCLC were identified by examination of methylation profiles and alterations of EGFR signaling. In consideration of the high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a distinct population of smoke-related NSCLC, the genetic profile of which is quite different from non-COPD NSCLC. 相似文献87.
A 65-year-old man presented to the emergency department complaining of right lower abdominal pain. Abdominal computed tomography
showed a whirling pattern of fatty streaks and vessels in the greater omentum. From this typical finding, a diagnosis of omental
torsion was made immediately, which was confirmed by subsequent surgery. We report a case of surgically and pathologically
proven omental torsion that demonstrated a typical appearance on computed tomography and was diagnosed preoperatively.
Part of this article was presented at the Japan Radiological Society meeting in October 2005 相似文献
88.
Akatsu H Yamagata HD Kawamata J Kamino K Takeda M Yamamoto T Miki T Tooyama I Shimohama S Kosaka K 《Dementia and geriatric cognitive disorders》2006,22(3):216-222
BACKGROUND/AIM: Brain-derived neurotrophic factor (BDNF) is associated with the hippocampus and the nigrostriatal dopaminergic function. Data showing that its level was reduced in Alzheimer's disease (AD) and Parkinson's disease (PD) suggested that the BDNF function must play an important role in the pathogenetics of these diseases. Indeed, variation in the BDNF gene may confer susceptibility to AD and PD development. Recently, a functional BDNF Val66Met polymorphism has been found to be associated with episodic memory and hippocampal function, with intracellular trafficking, and with activity-dependent secretion of BDNF. To date, there have been several conflicting reports on the correlation between AD or PD and Val66Met or C270T polymorphism in the BDNF promoter region, although no data on this relationship have been published with respect to dementia with Lewy bodies (DLB). In the present study, we investigated a possible association between such BDNF polymorphisms and susceptibility to AD or DLB. METHODS: BDNF genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism method in autopsy-confirmed human samples. RESULTS AND CONCLUSION: On comparing patients and controls, the distribution of BDNF genotypes and alleles did not differ significantly. Our findings suggest that it is unlikely that these BDNF polymorphisms play a major role in the pathogenesis of AD and DLB in the Japanese population. 相似文献
89.
90.
Saeki H Hattori N Mitsui H Adachi M Imakado S Ishibashi Y Tamaki K 《The Journal of dermatology》2002,29(3):168-171
We described a 19-year old Japanese female with bullous congenital ichthyosiform erythroderma (BCIE) and examined the keratin gene mutation. Physical examination disclosed generalized erythema, ichthyosiform skin with scales, and erosions without palmoplantar keratoderma. Histological examination revealed hyperkeratosis with vacuolar degeneration in the granular layer of the epidermis. Sequence analysis demonstrated a C to G transition at the first position of codon 156 in the keratin 10 gene. The amino acid at codon 156 was deduced to have changed from arginine to cystine. Substitution from arginine to cysteine at codon 156 of the K 10 gene is assumed to be fatal for keratin filament assembly regardless of racial or ethnic difference. 相似文献