全文获取类型
收费全文 | 3383篇 |
免费 | 249篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 41篇 |
儿科学 | 106篇 |
妇产科学 | 90篇 |
基础医学 | 434篇 |
口腔科学 | 65篇 |
临床医学 | 293篇 |
内科学 | 814篇 |
皮肤病学 | 49篇 |
神经病学 | 227篇 |
特种医学 | 90篇 |
外科学 | 580篇 |
综合类 | 53篇 |
预防医学 | 264篇 |
眼科学 | 65篇 |
药学 | 232篇 |
中国医学 | 20篇 |
肿瘤学 | 222篇 |
出版年
2023年 | 29篇 |
2022年 | 75篇 |
2021年 | 111篇 |
2020年 | 75篇 |
2019年 | 117篇 |
2018年 | 130篇 |
2017年 | 69篇 |
2016年 | 77篇 |
2015年 | 100篇 |
2014年 | 133篇 |
2013年 | 169篇 |
2012年 | 235篇 |
2011年 | 239篇 |
2010年 | 148篇 |
2009年 | 116篇 |
2008年 | 177篇 |
2007年 | 168篇 |
2006年 | 155篇 |
2005年 | 152篇 |
2004年 | 152篇 |
2003年 | 122篇 |
2002年 | 113篇 |
2001年 | 41篇 |
2000年 | 54篇 |
1999年 | 54篇 |
1998年 | 25篇 |
1997年 | 19篇 |
1996年 | 28篇 |
1995年 | 21篇 |
1994年 | 20篇 |
1993年 | 21篇 |
1992年 | 40篇 |
1991年 | 35篇 |
1990年 | 33篇 |
1989年 | 48篇 |
1988年 | 45篇 |
1987年 | 35篇 |
1986年 | 32篇 |
1985年 | 30篇 |
1984年 | 23篇 |
1983年 | 20篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 15篇 |
1979年 | 25篇 |
1978年 | 22篇 |
1977年 | 12篇 |
1976年 | 7篇 |
1974年 | 11篇 |
1973年 | 11篇 |
排序方式: 共有3645条查询结果,搜索用时 15 毫秒
51.
Abeer Ahmed Rushdy Mona Ibrahim Mabrouk Ferialla Abdel-Hamid Abu-Sef Zeinab Hassan Kheiralla Said Mohamed Abdel -All Neveen Mohamed Saleh 《The Brazilian journal of infectious diseases》2013,17(4):431-437
ObjectivesTo study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates.MethodsAntimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated.ResultsFive Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F). Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2–4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC.ConclusionsEfflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gram-negative clinical isolates. 相似文献
52.
Mutation and protein expression of p53 in acquired immunodeficiency syndrome-related lymphomas 总被引:4,自引:0,他引:4
p53 mutations are found in a variety of neoplasia. B-immunoblastic lymphoma (BIBL) is a rapidly progressive, aggressive lymphoma. As patients with acquired immunodeficiency syndrome (AIDS) live longer, BIBL is becoming an increasing problem. We asked three questions in our study. What is the frequency of p53 mutations in BIBL? Is it more frequent in patients with AIDS? Can immunohistochemical staining of lymph nodes for expression of p53 substitute for mutational analysis of p53 to detect lymphomas with mutated p53? Exons 5, 6, 7, 8 of the p53 gene (hot-spots for mutations) were amplified and examined for mutations by single-strand conformation polymorphism (SSCP) analysis. Altered migration was observed in 7 of 52 BIBL samples. Of these, 4 of 25 were from individuals infected with human immunodeficiency virus (HIV) and 3 of 27 were not infected with HIV. Direct sequencing of amplified material confirmed the presence of mutations in exons 5, 7, 8 of p53. A total of 26 BIBL as well as other lymphoma/leukemia samples, stained strongly by immunohistochemistry with three antibodies directed against human p53. Five of 6 BIBL samples with p53 mutations stained strongly for p53, but 20 lymphoma samples with no detectable p53 mutations also stained strongly for p53. Of note, however, 10 hyperplastic, nonmalignant lymph nodes from individuals either infected or not infected with HIV had negligible staining for p53 protein. In conclusion, p53 mutations occur in about 14% BIBL samples; the frequency of p53 mutations in BIBL in individuals with and without AIDS was similar. Positive p53 immunohistochemistry did not correlate with detectable p53 mutations in the same tissue, but positive immunohistochemical staining for p53 was only found in neoplastic lymph nodes. This latter finding provides a strong warning that p53 immunochemistry with available reagents cannot be used to determine which tumors have mutations of p53. 相似文献
53.
Effect of small bowel resection on the intestinal surface acid microclimate in the rat 总被引:1,自引:0,他引:1
The effect of extensive (65%) proximal and middle small bowel resection on the intestinal surface acid microclimate (ISAM) of the remaining ileum in the rat was examined and the results were compared to those of sham-operated rats. ISAM pH measurements were performed in vivo using a pH microelectrode; incubation was performed in Krebs-Ringer phosphate buffer (pH 7.40 +/- 0.02). In the resected rats, ISAM pH of 6.03 +/- 0.07 and 7.22 +/- 0.03 were recorded in the proximal and distal part of the remaining ileum, respectively. In the sham-operated rats, ISAM pH of 6.04 +/- 0.07, 6.98 +/- 0.03 and 7.28 +/- 0.02 were recorded in the proximal jejunum and in the proximal and distal part of the corresponding ileal segment. ISAM pH was significantly lower (p less than 0.01) in the proximal part of the remaining ileum of the resected rats as compared to the corresponding part in the sham-operated rats but was similar in distal ileum. In fact, the ISAM pH of the proximal part of the remaining ileum of resected rats was as acidic as that of the jejunum of the sham-operated rats. These results clearly demonstrate that adaptation in the ISAM occurs in the remaining ileum following extensive resection of proximal and middle small intestine. 相似文献
54.
Abdallah El Sabbagh Mackram F. Eleid Mohammed Al-Hijji Nandan S. Anavekar David R. Holmes Vuyisile T. Nkomo Gustavo S. Oderich Stephen D. Cassivi Sameh M. Said Charanjit S. Rihal Jane M. Matsumoto Thomas A. Foley 《Current cardiology reports》2018,20(6):47
Purpose of Review
To highlight the various applications of 3D printing in cardiovascular disease and discuss its limitations and future direction.Recent Findings
Use of handheld 3D printed models of cardiovascular structures has emerged as a facile modality in procedural and surgical planning as well as education and communication.Summary
Three-dimensional (3D) printing is a novel imaging modality which involves creating patient-specific models of cardiovascular structures. As percutaneous and surgical therapies evolve, spatial recognition of complex cardiovascular anatomic relationships by cardiologists and cardiovascular surgeons is imperative. Handheld 3D printed models of cardiovascular structures provide a facile and intuitive road map for procedural and surgical planning, complementing conventional imaging modalities. Moreover, 3D printed models are efficacious educational and communication tools. This review highlights the various applications of 3D printing in cardiovascular diseases and discusses its limitations and future directions.55.
Ligands for peroxisome proliferator-activated receptorγ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice 下载免费PDF全文
Elena Elstner Carsten Müller Kozo Koshizuka Elizabeth A. Williamson Dorothy Park Hiroya Asou Peter Shintaku Jonathan W. Said David Heber H. Phillip Koeffler 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(15):8806-8811
Induction of differentiation and apoptosis in cancer cells through ligands of nuclear hormone receptors (NHRs) is a novel and promising approach to cancer therapy. All-trans-retinoic acid (ATRA), an RA receptor-specific NHR ligand, is now used for selective cancers. The NHR, peroxisome proliferator-activated receptor γ (PPARγ) is expressed in breast cancer cells. Activation of PPARγ through a synthetic ligand, troglitazone (TGZ), and other PPARγ-activators cause inhibition of proliferation and lipid accumulation in cultured breast cancer cells. TGZ (10−5 M, 4 days) reversibly inhibits clonal growth of MCF7 breast cancer cells and the combination of TGZ (10−5 M) and ATRA (10−6 M, 4 days) synergistically and irreversibly inhibits growth and induces apoptosis of MCF7 cells, associated with a dramatic decrease of their bcl-2 protein levels. Similar effects are noted with in vitro cultured breast cancer tissues from patients, but not with normal breast epithelial cells. The observed apoptosis mediated by TGZ and ATRA may be related to the striking down-regulation of bcl-2, because forced over-expression of bcl-2 in MCF7 cells cultured with TGZ and ATRA blocks their cell death. TGZ significantly inhibits MCF7 tumor growth in triple immunodeficient mice. Combined administration of TGZ and ATRA causes prominent apoptosis and fibrosis of these tumors without toxic effects on the mice. Taken together, this combination may provide a novel, nontoxic and selective therapy for human breast cancers. 相似文献
56.
57.
Reem J. Al Argan Safi G. Alqatari Abir H. Al Said Raed M. Alsulaiman Abdulsalam Noor Lameyaa A. Al Sheekh Fedaa H. Al Beladi 《Medicine》2021,100(19)
Introduction:Corona virus disease-2019 (COVID-19) presents primarily with respiratory symptoms. However, extra respiratory manifestations are being frequently recognized including gastrointestinal involvement. The most common gastrointestinal symptoms are nausea, vomiting, diarrhoea and abdominal pain. Gastrointestinal perforation in association with COVID-19 is rarely reported in the literature.Patient concerns and diagnosis:In this series, we are reporting 3 cases with different presentations of gastrointestinal perforation in the setting of COVID-19. Two patients were admitted with critical COVID-19 pneumonia, both required intensive care, intubation and mechanical ventilation. The first one was an elderly gentleman who had difficult weaning from mechanical ventilation and required tracheostomy. During his stay in intensive care unit, he developed Candidemia without clear source. After transfer to the ward, he developed lower gastrointestinal bleeding and found by imaging to have sealed perforated cecal mass with radiological signs of peritonitis. The second one was an obese young gentleman who was found incidentally to have air under diaphragm. Computed tomography showed severe pneumoperitoneum with cecal and gastric wall perforation. The third case was an elderly gentleman who presented with severe COVID-19 pneumonia along with symptoms and signs of acute abdomen who was confirmed by imaging to have sigmoid diverticulitis with perforation and abscess collection.Interventions:The first 2 cases were treated conservatively. The third one was treated surgically.Outcome:Our cases had a variable hospital course but fortunately all were discharged in a good clinical condition.Conclusion:Our aim from this series is to highlight this fatal complication to clinicians in order to enrich our understanding of this pandemic and as a result improve patients’ outcome. 相似文献
58.
Hiba Hadj Ammar Sirine Lajili Rafik Ben Said Didier Le Cerf Abderrahman Bouraoui Hatem Majdoub 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2015,23(1)
Background
Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities.Methods
The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl.Results
The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity.Conclusion
The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising. 相似文献59.
Horvath Steve Lin David T. S. Kobor Michael S. Zoller Joseph A. Said Jonathan W. Morgello Susan Singer Elyse Yong William H. Jamieson Beth D. Levine Andrew J. 《Age (Dordrecht, Netherlands)》2022,44(3):1609-1620
GeroScience - Epigenetic clocks based on patterns of DNA methylation have great importance in understanding aging and disease; however, there are basic questions to be resolved in their... 相似文献
60.