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Tai-Seung Nam Jin Hee Kim Chi-Hsuan Chang Woong Yoon Yoon Seok Jung Sa-Yoon Kang Boo Ahn Shin Ming-Der Perng Seok-Yong Choi Myeong-Kyu Kim 《European journal of human genetics : EJHG》2015,23(1):72-78
Alexander disease (AxD) is an astrogliopathy that primarily affects the white matter of the central nervous system (CNS). AxD is caused by mutations in a gene encoding GFAP (glial fibrillary acidic protein). The GFAP mutations in AxD have been reported to act in a gain-of-function manner partly because the identified mutations generate practically full-length GFAP. We found a novel nonsense mutation (c.1000 G>T, p.(Glu312Ter); also termed p.(E312*)) within a rod domain of GFAP in a 67-year-old Korean man with a history of memory impairment and leukoencephalopathy. This mutation, GFAP p.(E312*), removes part of the 2B rod domain and the whole tail domain from the GFAP. We characterized GFAP p.(E312*) using western blotting, in vitro assembly and sedimentation assay, and transient transfection of human adrenal cortex carcinoma SW13 (Vim+) cells with plasmids encoding GFAP p.(E312*). The GFAP p.(E312*) protein, either alone or in combination with wild-type GFAP, elicited self-aggregation. In addition, the assembled GFAP p.(E312*) aggregated into paracrystal-like structures, and GFAP p.(E312*) elicited more GFAP aggregation than wild-type GFAP in the human adrenal cortex carcinoma SW13 (Vim+) cells. Our findings are the first report, to the best of our knowledge, on this novel nonsense mutation of GFAP that is associated with AxD and paracrystal formation. 相似文献
23.
Andel R Crowe M Pedersen NL Fratiglioni L Johansson B Gatz M 《The journals of gerontology. Series A, Biological sciences and medical sciences》2008,63(1):62-66
BACKGROUND: With the number of people with dementia increasing, identifying potential protective factors has become more important. We explored the association between physical exercise at midlife and subsequent risk of dementia among members of the HARMONY study. METHODS: Measures of exercise were obtained by the Swedish Twin Registry an average of 31 years prior to dementia assessment. Dementia was diagnosed using a two-stage procedure--screening for cognitive impairment followed by full clinical evaluation. We used two study designs: case-control analyses included 264 cases with dementia (176 had Alzheimer's disease) and 2870 controls; co-twin control analyses included 90 twin pairs discordant for dementia. RESULTS: In case-control analyses, controlling for age, sex, education, diet (eating fruits and vegetables), smoking, drinking alcohol, body mass index, and angina, light exercise such as gardening or walking and regular exercise involving sports were associated with reduced odds of dementia compared to hardly any exercise (odds ratio [OR] = 0.63, 95% confidence interval [CI], 0.43-0.91 for light exercise; OR = 0.34, 95% CI, 0.16-0.72 for regular exercise). Findings were similar for Alzheimer's disease alone. In co-twin control analyses, controlling for education, the association between higher levels of exercise and lower odds of dementia approached significance (OR = 0.50, 95% CI, 0.23-1.06; p =.072). CONCLUSIONS: Exercise at midlife may reduce the odds of dementia in older adulthood, suggesting that exercise interventions should be explored as a potential strategy for delaying disease onset. 相似文献
24.
Chandra A. Reynolds Catalina Zavala Margaret Gatz Loryana Vie Boo Johansson Bo Malmberg Erik Ingelsson Jonathan A. Prince Nancy L. Pedersen 《Neurobiology of aging》2013
The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women. 相似文献
25.
26.
Jae Kyun Choi Soomin Ahn Jai Young Cho YoungRok Choi Ho‐Seong Han Boo‐ok Jang Gwang Hyeon Choi Eun Sun Jang Jin‐Wook Kim Sook‐Hyang Jeong 《Transplant infectious disease》2020,22(3)
Acute hepatitis E virus (HEV) infection could lead to acute liver failure (ALF), which requires liver transplantation (LT). HEV infection could progress to chronic infection in an immunosuppressed host. De novo autoimmune hepatitis (AIH) is a rare occurrence of AIH during post‐LT immunosuppressive therapy in patients who underwent LT due to not AIH but some other etiology. Here, we report the first case of ALF due to HEV infection, the recurrence of HEV after LT that responded to ribavirin therapy, and then the development of de novo AIH showing a complete response to glucocorticoid therapy but multiple relapses after steroid withdrawal. This peculiar case suggests that HEV could have a pathogenic role in the development of the de novo AIH; additionally, this case report could help clinicians make therapeutic decisions in the post‐LT condition. 相似文献
27.
Sung Woo Ryu Gene Hyun Bok Jae Young Jang Soung Won Jeong Nam Seok Ham Ji Hye Kim Eui Ju Park Jin Nyoung Kim Woong Cheul Lee Kwang Yeun Shim Sae Hwan Lee Sang Gyune Kim Sang-Woo Cha Young Seok Kim Young Deok Cho Hong Soo Kim Boo Sung Kim 《Gut and liver》2014,8(3):292-297
Background/Aims
To evaluate the diagnostic value of contrast (SonoVue®) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses.Methods
CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI.Results
The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with κ values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a κ value of 0.765.Conclusions
If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses. 相似文献28.
Jeong SW Jang JY Lee TH Kim HG Hong SW Park SH Kim SG Cheon YK Kim YS Cho YD Kim JO Kim BS Lee EJ Kim TH 《Journal of gastroenterology and hepatology》2012,27(2):248-255
Background and Aim: Colonic mucosal defects might be a route for bacterial invasion into the portal system, with subsequent hematogenous spread to the liver. We retrospectively investigated the results of colonoscopy and the clinical characteristics of patients with pyogenic liver abscess of colonic origin. Methods: A total of 230 consecutive patients with pyogenic liver abscess were reviewed between 2003 and 2010. The 230 patients were categorized into three groups (pancreatobiliary [n = 135], cryptogenic [n = 81], and others [n = 14]). Of the 81 cryptogenic patients, 37 (45.7%) underwent colonoscopy. Colonic lesions with mucosal defects were considered colonic causes of abscess. Results: In the 37 colonoscopic investigations, colon cancer was found in six patients (16.2%), laterally‐spreading tumor (LST) in two patients (5.4%), multiple colon ulcers in one patient (2.7%), colon polyps in 17 patients (45.9%), and diverticula in four patients (10.8%). Nine (11%) of 81 cryptogenic abscesses were therefore reclassified as being of colonic origin (colon cancer = 6, LST = 2, ulcer = 1). Three cases were stage III colon cancer, and the others were stage I. Two LST were high‐grade dysplasia. The percentage of patients with Klebsiella pneumoniae (K. pneumoniae) and diabetes mellitus (DM) of colonic origin was 66.7%, which was significantly higher than the 8.6% for other causes (P < 0.001). Conclusions: Of the 37 patients with cryptogenic pyogenic liver abscess who underwent colonoscopy, nine (24.3%) were diagnosed with a colonic cause. Colonoscopy should be considered for the detection of hidden colonic malignant lesions in patients with cryptogenic pyogenic liver abscess, especially for patients with K. pneumoniae and DM. 相似文献
29.
AIM: To compare the non-invasive tear film break-up time (NIBUT), tear break up time (TBUT), basal tear secretion (BTS) and blink rate in four ethnic groups: Malay, Chinese, Indian and Nigerian.
METHODS: Totally 120 healthy (61 males and 59 females) subjects (without dry eye symptoms and ocular surface disorder) with the age 20 to 39 years were recruited; 30 were Malays, 30 were Chinese, 31 were Indians and 29 were Nigerians. Based on McMonnies questionnaire and clinical examination, normal subjects were selected. NIBUT, TBUT, BTS were assessed in only one eye (right) of each subject and blink rate was also assessed.
RESULTS: There was significant difference in the NIBUT, TBUT, BTS and blink rate among 4 different ethnic groups (P=0.018, 0.001, 0.011, and 0.004 respectively). No statistically significant difference of NIBUT, TBUT, BTS and blink rate was found between the genders among different ethnic groups. Indian had higher median for NIBUT (10±6s), TBUT (7±5s) and BTS (20±20 mm) than other races. Chinese had lower median for NIBUT (7.5±4s) and TBUT (4±2s) while Malay had for BTS (9.5±16 mm) among the groups. There was no significant correlation of blink rate with NIBUT (r=-0.119, P=0.195), TBUT (r=-0.086, P=0.352), and BTS (r=-0.123, P=0.180) respectively.
CONCLUSION: The tear-film measurement values are variability in four ethnic groups. 相似文献
30.
Characterization and quantitation of the circulating forms of serum transferrin receptor using domain-specific antibodies 总被引:1,自引:0,他引:1
To characterize the nature of the immunoreactive transferrin receptor in human serum, antisera were developed to peptide sequences of the extracellular domain of human transferrin receptor between amino acids 107 and 120 and the intracellular domain between amino acids 40 and 54. Antisera against the extracellular domain exhibited reactivity against both purified intact receptor and immunopurified circulating receptor, whereas antisera against the intracellular domain reacted only with intact receptor. Using competitive binding enzyme-linked immunosorbent assays, transferrin receptor in ultracentrifuged sera from normal subjects and patients with sickle cell anemia could be detected with antisera against the extracellular but not the intracellular domain. When the pellet obtained by ultracentrifugation of these sera was assayed after solubilization in 1% teric (polyoxyethylene-9-lauryl ether), only 0.6% of total serum receptor was detected in normal subjects and 3.8% in subjects with sickle cell disease. Roughly equal amounts of this pelleted immunoactivity were detected with antibodies against the extracellular and intracellular domains. These results indicate that less than 1% of transferrin receptor in normal human sera is intact receptor consistent with an exosomal origin and that virtually all circulating transferrin receptor is in the form of a truncated extracellular domain. 相似文献