全文获取类型
收费全文 | 3531篇 |
免费 | 197篇 |
国内免费 | 39篇 |
专业分类
耳鼻咽喉 | 20篇 |
儿科学 | 132篇 |
妇产科学 | 26篇 |
基础医学 | 383篇 |
口腔科学 | 31篇 |
临床医学 | 256篇 |
内科学 | 987篇 |
皮肤病学 | 21篇 |
神经病学 | 188篇 |
特种医学 | 174篇 |
外科学 | 920篇 |
综合类 | 5篇 |
预防医学 | 79篇 |
眼科学 | 47篇 |
药学 | 129篇 |
中国医学 | 7篇 |
肿瘤学 | 362篇 |
出版年
2024年 | 6篇 |
2023年 | 27篇 |
2022年 | 59篇 |
2021年 | 100篇 |
2020年 | 53篇 |
2019年 | 72篇 |
2018年 | 98篇 |
2017年 | 67篇 |
2016年 | 99篇 |
2015年 | 77篇 |
2014年 | 108篇 |
2013年 | 135篇 |
2012年 | 215篇 |
2011年 | 207篇 |
2010年 | 147篇 |
2009年 | 141篇 |
2008年 | 200篇 |
2007年 | 238篇 |
2006年 | 231篇 |
2005年 | 197篇 |
2004年 | 232篇 |
2003年 | 221篇 |
2002年 | 222篇 |
2001年 | 44篇 |
2000年 | 53篇 |
1999年 | 42篇 |
1998年 | 50篇 |
1997年 | 45篇 |
1996年 | 39篇 |
1995年 | 31篇 |
1994年 | 37篇 |
1993年 | 36篇 |
1992年 | 31篇 |
1991年 | 39篇 |
1990年 | 27篇 |
1989年 | 17篇 |
1988年 | 11篇 |
1987年 | 12篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 5篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1974年 | 6篇 |
1972年 | 6篇 |
1970年 | 4篇 |
排序方式: 共有3767条查询结果,搜索用时 31 毫秒
61.
Yang Liu Yoshifumi Baba Takatsugu Ishimoto Hiroyasu Tsutsuki Tianli Zhang Daichi Nomoto Kazuo Okadome Kensuke Yamamura Kazuto Harada Kojiro Eto Yukiharu Hiyoshi Masaaki Iwatsuki Yohei Nagai Shiro Iwagami Yuji Miyamoto Naoya Yoshida Yoshihiro Komohara Masaki Ohmuraya Xiaoming Wang Jaffer A. Ajani Tomohiro Sawa Hideo Baba 《British journal of cancer》2021,124(5):963
Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.Subject terms: Tumour biomarkers, Oesophageal cancer 相似文献
62.
63.
Kotaro Shimizu Atsuhiko Uno Kazuya Takemura Naoki Ashida Ryohei Oya Takahiro Kitamura Yukinori Takenaka Yoshifumi Yamamoto 《Auris, nasus, larynx》2018,45(3):640-643
Laryngeal cleft is an anomaly of failed posterior closure of the larynx. Most cases are diagnosed and need treatment early in life due to respiratory and swallowing problems. We report an unusual case of a 66-year-old man with an asymptomatic laryngeal cleft until treatment for hypopharyngeal cancer. During concurrent chemoradiotherapy (CCRT), despite reduced tumor volume, he presented severe dysphagia and dyspnea, followed by severe pneumonia twice. Because CCRT had to be discontinued, a pharyngolaryngectomy was performed for the cancer treatment. The resected specimen showed total removal of the tumor and a total longitudinal cleft of the cricoid cartilage, classified as a type III laryngeal cleft by the Benjamin and Inglis’ classification. A review of computed tomography images indicated that the redundant mucosa from bilateral edges closed the separation of the posterior cricoid cartilage and narrowed the laryngeal airway during CCRT. Adult presentations of laryngeal cleft are quite rare with only ten reported cases in English literature; the present case is of the oldest patient. Undiagnosed cases with laryngeal cleft may exist asymptomatically or without severe symptoms. The awareness of this condition may increase its diagnosis as a cause of diseases such as aspiration and recurrent pneumonia even in adult patients. 相似文献
64.
65.
The aim of this study was to evaluate potential predictive factors in the treatment of limited-disease small cell lung cancer (LD-SCLC). A total of 33 patients with LD-SCLC who underwent definitive chemoradiotherapy at our institute between April 1996 and May 2007 were enrolled in our retrospective study. The relationship between a range of potential predictive factors and the initial response, time to progression and pattern of failure was analyzed. The factors evaluated included the tumor markers Pro-gastrin-releasing peptide (Pro-GRP) and neuron-specific enolase; net tumor size (sum of each lesion mass on computed tomography at 1-cm intervals); total radiation dose; biological effective dose (BED); overall treatment time (OTT); time between the start of any type of treatment and the end of radiation therapy (SER). In addition, the novel factors of radiation dose-intensity (RDI = BED/OTT) and RDI/NTS (= RDI/net tumor size) were defined. Of the 33 patients evaluated in our study, 22 (67%) achieved a complete response (CR) and 27 (82%) experienced treatment failure or recurrence. High RDI/NTS values showed a significant correlation with CR (P=0.043). Prolonged OTT and lower values of RDI and RDI/NTS showed a significant correlation with recurrence within 12 months (P=0.022, 0.033 and 0.015, respectively). The lower values of RDI and RDI/NTS showed a significant correlation with distant metastasis as a first failure site (P=0.038 and 0.044, respectively). Patients with RDI/NTS ≥0.08 had a more favorable prognosis (P=0.045). Thus, RDI and RDI/NTS may become beneficial predictive factors in the treatment of LD-SCLC. However, further studies are required to confirm our preliminary results. 相似文献
66.
Watanabe N Arai H Nishihara Y Taniguchi M Watanabe N Hunter T Osada H 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(13):4419-4424
Wee1, the Cdc2 inhibitory kinase, needs to be down-regulated at the onset of mitosis to ensure rapid activation of Cdc2. Previously, we have shown that human somatic Wee1 (Wee1A) is down-regulated both by protein phosphorylation and degradation, but the underlying mechanisms had not been elucidated. In the present study, we have identified the beta-transducin repeat-containing protein 1/2 (beta-TrCP1/2) F-box protein-containing SKP1/Cul1/F-box protein (SCF) complex (SCF(beta-TrCP1/2)) as an E3 ubiquitin ligase for Wee1A ubiquitination. Although Wee1A lacks a consensus DS(p)GXXS(p) phospho-dependent binding motif for beta-TrCP, recognition of Wee1A by beta-TrCP depended on phosphorylation, and two serine residues in Wee1A, S53 and S123, were found to be the most important phosphorylation sites for beta-TrCP recognition. We have found also that the major M-phase kinases polo-like kinase 1 (Plk1) and Cdc2 are responsible for the phosphorylation of S53 and S123, respectively, and that in each case phosphorylation generates an unconventional phospho-degron (signal for degradation) that can be recognized by beta-TrCP. Phosphorylation of Wee1A by these kinases cooperatively stimulated the recognition and ubiquitination of Wee1A by SCF(beta-TrCP1/2) in vitro. Mutation of these residues or depletion of beta-TrCP by small-interfering RNA treatment increased the stability of Wee1A in HeLa cells. Moreover, our analysis indicates that beta-TrCP-dependent degradation of Wee1A is important for the normal onset of M-phase in vivo. These results also establish the existence of a feedback loop between Cdc2 and Wee1A in somatic cells that depends on ubiquitination and protein degradation and ensures the rapid activation of Cdc2 when cells are ready to divide. 相似文献
67.
Yoshinaga M Anan R Nomura Y Tanaka Y Tanaka Y Sarantuya J Oku S Nishi S Kawano Y Tei C Arima K 《The American journal of cardiology》2004,94(9):1186-1189
The prevalence of Brugada's electrocardiographic (ECG) pattern in 7,022 male adolescents in the seventh grade was determined, and the same subjects were reexamined 3 years later, while in tenth grade. Two subjects (0.03%) and 7 subjects (0.10%) showed Brugada's ECG pattern by the conventional criterion (J point or ST-segment >/=0.1 mV in leads V(1) to V(3)), and no subjects (0%) and 2 subjects (0.03%) fulfilled the recent criterion (J point or ST-segment >/=0.2 mV) in the seventh and tenth grades, respectively, indicating that Brugada's ECG pattern begins to appear during junior high school and increases until late adulthood. 相似文献
68.
Analysis of K-<Emphasis Type="Italic">ras</Emphasis> Codon 12 Mutation in Flat and Nodular Variants of Serrated Adenoma in the Colon 总被引:4,自引:0,他引:4
Higashidani Y Tamura S Morita T Tadokoro T Yokoyama Y Miyazaki J Yang Y Takeuchi S Taguchi H Onishi S 《Diseases of the colon and rectum》2003,46(3):327-332
PURPOSE: The developmental process of serrated adenomas is obscure, and the importance of genetic alterations has not been elucidated clearly. The possibility that the developmental process and genetic alterations of serrated adenomas could differ from those of ordinary tubular adenomas was explored in this work.
METHODS: Serrated adenomas were obtained by endoscopic resection (n = 57) and divided into two groups: flat (n = 10) and nodular (n = 47). Mutation of the K-ras gene was analyzed by enriched polymerase chain reaction–enzyme-linked mini-sequence assay, which can detect not only the presence of a mutation but also the mutation type of K-ras codon 12 with high sensitivity. Methylation-specific polymerase chain reaction was performed with specific primers for the DNA repair gene O6-methylguanine-DNA methyltransferase.
RESULTS: Serrated adenomas located in the rectum were more likely to have a K-ras mutation (9/12, 75 percent), whereas serrated adenomas of the flat type were less likely to have one (1/10, 10 percent). Furthermore, nodular serrated adenomas that occurred in the rectum possessed a high frequency of K-ras gene codon 12 point mutation (8/10, 80 percent) despite an overall frequency of 46.8 percent (22/47). A mutation of the K-ras codon 12 gene was detected in 23 (40.4 percent) of 57 serrated adenomas. Three types of point mutations of codon 12 were detected, with the mutation of GAT being observed most frequently.
CONCLUSIONS: This study shows that development of nodular serrated adenomas may depend on the mutation of the K-ras codon 12 gene, whereas development of flat serrated adenomas may not. Additionally, serrated adenomas that occur in the rectum are closely related to the mutation of the K-ras codon 12 gene. K-ras mutations in serrated adenomas may be unaffected by the epigenetic silencing of O6-methylguanine-DNA methyltransferase by promoter hypermethylation. 相似文献
69.
Yamagishi H Koike T Ohara S Kobayashi S Ariizumi K Abe Y Iijima K Imatani A Inomata Y Kato K Shibuya D Aida S Shimosegawa T 《World journal of gastroenterology : WJG》2008,14(9):1358-1364
AIM:To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms in a large unselected general population in Japan.
METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged 〉 40 years. A total of 160 983 Japanese (60 774 male, 100 209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 (34 275 male, 48 619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period.
RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year agegroup. Dysphagia was also significantly more frequent in female patients.
CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group. 相似文献
METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged 〉 40 years. A total of 160 983 Japanese (60 774 male, 100 209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 (34 275 male, 48 619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period.
RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year agegroup. Dysphagia was also significantly more frequent in female patients.
CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group. 相似文献
70.
Shugo Mizuno Takashi Yano Shuji Isaji Shunichi Nakagawa Hajime Yokoi Yoshifumi Kawarada 《Journal of hepato-biliary-pancreatic sciences》1997,4(4):474-479
A 70-year-old woman with gastric cancer was referred to our hospital for further evaluation of a cystic mass in the head of the pancreas. Endoscopic ultrasonography (EUS) showed a mural nodule in the cystic mass. Endoscopic retrograde cholangio pancreatography (ERCP) revealed a cystic lesion with a filling defect caused by obstruction with mucus. Magnetic resonance cholangiopancreatography (MRCP) allowed visualization of the entire configuration of the cystic lesion despite the presence of mucus. Pancreatic juice was positive for K-ras point mutation. Pancreatoduodenectomy was performed, with a diagnosis of intraductal papillary adenoma or adenocarcinoma with gastric cancer. Pancreatography of the resected specimen showed a cystic lesion in the uncinate process, consistent with the MRCP findings. Histological examination revealed an intraductal papillary adenoma. MRCP is very useful for demonstrating the total configuration of cystic lesions and is not impeded by impacted mucin. Nevertheless, because of its lower spatial resolution, this noninvasive modality is of limited value in detecting mural nodules. At present, therefore, surgical indications for cystic lesion of the pancreas should be determined by comprehensively analyzing: size and sequential changes in size of the cyst; presence of mural nodules, cytologic examination for presence of malignant cells, and/or K-ras point mutation in pure pancreatic juice. 相似文献