全文获取类型
收费全文 | 258篇 |
免费 | 10篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 1篇 |
妇产科学 | 1篇 |
基础医学 | 24篇 |
临床医学 | 28篇 |
内科学 | 102篇 |
皮肤病学 | 5篇 |
神经病学 | 19篇 |
特种医学 | 3篇 |
外科学 | 38篇 |
综合类 | 1篇 |
预防医学 | 16篇 |
眼科学 | 2篇 |
药学 | 12篇 |
肿瘤学 | 22篇 |
出版年
2023年 | 1篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 5篇 |
2013年 | 17篇 |
2012年 | 16篇 |
2011年 | 14篇 |
2010年 | 10篇 |
2009年 | 4篇 |
2008年 | 12篇 |
2007年 | 8篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 9篇 |
2003年 | 10篇 |
2002年 | 11篇 |
2001年 | 11篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 9篇 |
1991年 | 10篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1969年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有275条查询结果,搜索用时 343 毫秒
51.
Bravo FJ Bernstein DI Beadle JR Hostetler KY Cardin RD 《Antimicrobial agents and chemotherapy》2011,55(1):35-41
Cytomegalovirus (CMV) infection is the leading cause of congenital infection, producing both sensorineural hearing loss and mental retardation. We evaluated the in vivo efficacy of an orally bioavailable analog of cidofovir, hexadecyloxypropyl-cidofovir (HDP-CDV), against guinea pig CMV (GPCMV) in a guinea pig model of congenital CMV infection. HDP-CDV exhibited antiviral activity against GPCMV with a 50% effective concentration (EC(50)) of 0.004 μM ± 0.001 μM. To evaluate in vivo efficacy, pregnant Hartley guinea pigs were inoculated with GPCMV during the late second/early third trimester of gestation. Animals were administered 20 mg HDP-CDV/kg body weight orally at 24 h postinfection (hpi) and again at 7 days postinfection (dpi) or administered 4 mg/kg HDP-CDV orally each day for 5 days or 9 days. Virus levels in dam and pup tissues were evaluated following delivery, or levels from dam, placenta, and fetal tissues were evaluated following sacrifice of dams at 10 dpi. All HDP-CDV regimens significantly improved pup survival, from 50 to 60% in control animals to 93 to 100% in treated animals (P ≤ 0.019). Treatment with 20 mg/kg HDP-CDV significantly reduced the viral load in pup spleen (P = 0.017) and liver (P = 0.029). Virus levels in the placenta were significantly reduced at 10 dpi following daily treatment with 4 mg/kg HDP-CDV for 5 or 9 days. The 9-day treatment also significantly reduced the viral levels in the dam spleen and liver. Although the 4-mg/kg treatment improved pup survival, virus levels in the fetal tissues were similar to those in control tissues. Taken together, HDP-CDV shows potential as a well-tolerated antiviral candidate for treatment of congenital human CMV (HCMV) infection. 相似文献
52.
Oxidative damage, pro-inflammatory cytokines, TGF-α and c-myc in chronic HCV-related hepatitis and cirrhosis 总被引:6,自引:0,他引:6
Farinati F Cardin R Bortolami M Guido M Rugge M 《World journal of gastroenterology : WJG》2006,12(13):2065-2069
AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-alpha and c-myc. METHODS: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-alpha, IL-1beta, TGF-alpha and c-myc in liver specimens was detected by semi-quantitative comparative RT-PCR. RESULTS: TNF-alpha levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1beta was higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-alpha and staging (P=0.05) and between IL-1beta levels and grading (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-alpha expression and HCV genotype (P=0.02). CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-alpha levels. As HCV-related liver damage progresses, TNF-alpha levels drop while IL-1beta and c-myc levels increase, which may be relevant to liver carcinogenesis. 相似文献
53.
Laval G Arvieux C Stefani L Villard ML Mestrallet JP Cardin N 《Journal of pain and symptom management》2006,31(6):502-512
A prospective protocol for treatment of malignant inoperable bowel obstruction was implemented at Grenoble University Hospital Center for 4 years. All 80 episodes of obstruction resulted from peritoneal carcinomatosis and none could expect another treatment cure. The protocol comprised three successive stages. Stage I included treatment for 5 days with a corticosteroid, antiemetic, anticholinergic, and analgesic. Stage II provided a somatostatin analogue if vomiting persisted. After 3 days, Stage III provided a venting gastrostomy. Obstruction relief with symptom control was obtained by medical treatment in 29 cases and symptom control occurred alone in an additional 32 cases. Ten patients were relieved by venting gastrostomy. Symptom control without permanent nasogastric tube (NGT) placement occurred in 72 episodes (90%). Eight patients with refractory vomiting were obliged to continue the NGT until death. Fifty-eight obstruction episodes (73%) were controlled in 10 days or less. Median time before gastrostomy was 17 days. Median survival was 31 days. This series suggests that a staged protocol for the treatment of inoperable malignant bowel obstruction is highly effective in relieving symptoms. A subgroup experiences relief of obstruction using this approach. 相似文献
54.
Niall Cardin Chris Holmes The Wellcome Trust Case Control Consortium Peter Donnelly Jonathan Marchini 《Genetic epidemiology》2011,35(6):536-548
Accurate assignment of copy number at known copy number variant (CNV) loci is important for both increasing understanding of the structural evolution of genomes as well as for carrying out association studies of copy number with disease. As with calling SNP genotypes, the task can be framed as a clustering problem but for a number of reasons assigning copy number is much more challenging. CNV assays have lower signal‐to‐noise ratios than SNP assays, often display heavy tailed and asymmetric intensity distributions, contain outlying observations and may exhibit systematic technical differences among different cohorts. In addition, the number of copy‐number classes at a CNV in the population may be unknown a priori. Due to these complications, automatic and robust assignment of copy number from array data remains a challenging problem. We have developed a copy number assignment algorithm, CNVCALL, for a targeted CNV array, such as that used by the Wellcome Trust Case Control Consortium's recent CNV association study. We use a Bayesian hierarchical mixture model that robustly identifies both the number of different copy number classes at a specific locus as well as relative copy number for each individual in the sample. This approach is fully automated which is a critical requirement when analyzing large numbers of CNVs. We illustrate the methods performance using real data from the Wellcome Trust Case Control Consortium's CNV association study and using simulated data. Genet. Epidemiol. 2011. © 2011 Wiley‐Liss, Inc. 35: 536‐548, 2011 相似文献
55.
Z Ben-Ari F Cardin A P McCormick G Wannamethee A K Burroughs 《Journal of hepatology》1999,31(3):443-450
BACKGROUND/AIMS: Variceal bleeding is a frequent complication of cirrhosis and is associated with a high risk of early rebleeding. In patients with peptic ulcers, continued bleeding or early rebleeding are risk factors for mortality and can be predicted by statistical models; however, no such models exist for acute variceal bleeding. METHODS: We prospectively evaluated failure to control bleeding in 695 consecutive patients with cirrhosis, admitted for haematemesis and/or melaena. Criteria were defined for failure to control bleeding, which comprised both continued bleeding or early rebleeding within 5 days of admission. There were 2 sequential groups of patients: (i) those with variceal bleeding initially treated with blood transfusion and vasoactive drugs, and if these failed followed by sclerotherapy (n = 385); (ii) those with variceal bleeding treated with injection sclerotherapy at diagnostic endoscopy (n = 144). The third group was those with bleeding from other sources related to portal hypertension (n = 166). RESULTS: Failure to control bleeding was noted in 169 (44%) patients in group 1, 55 (38%) in group 2 and 44 (25%) in group 3. Twenty variables that were evaluable within 6 h of admission, pertaining to severity of bleeding, severity of type of liver disease, mode of admission, and time of diagnostic endoscopy, were entered into a multivariate Cox model. Independent predictors of early rebleeding in group 1 were: active bleeding at endoscopy (irrespective of interval from admission) (p<0.0001), encephalopathy (p = 0.007), platelet count (p = 0.002), history of alcoholism (p = 0.002), presentation with haematemesis (p = 0.02), log urea (p = 0.03) and (shorter) interval to admission (p = 0.007). The variables predictive of 30-day mortality were: early bleeding (p<0.0007), bilirubin (p = 0.0006), encephalopathy (p<0.0001), (shorter) interval to admission (p<0.0001), and log urea (p = 0.004); a model based on these variables was also a good predictor of mortality in the other 2 groups. However, the model derived from group 1 for failure to control variceal bleeding was different in group 2, despite similar patient characteristics and a similar failure rate (following a single injection). This could suggest that sclerotherapy may induce bleeding in some patients independently of the baseline risk for failure to control bleeding. CONCLUSIONS: In cirrhotic patients who present with haematemesis or melaena, active variceal bleeding at diagnostic endoscopy is predictive of failure to control bleeding (continued bleeding or early rebleeding within 5 days of admission), and this failure is predictive of 30-day mortality. 相似文献
56.
M Ferrari M Armani P Melacini C Egloff G Scattolin G Fasoli G Cardin G Miraglia C Angelini S Dalla Volta 《Giornale italiano di cardiologia》1980,10(10):1288-1298
17 patients with myotonic dystrophy have been studied. The skeletal muscle disease has been assessed by history, physical examination, electro-myography and muscle biopsy. Cardiac evaluation has been obtained by history, physical examination, chest X-ray, ecg at rest and after exercise, vectorcardiography and echocardiography. Only two patients presented symptoms and clinical findings of cardiac disease, otherwise conduction disturbances have been founded in 15 cases, pseudoinfarct pattern in 5 cases and loss of anterior vectors in 2 cases. Has to be remembered that in myotonic dystrophy sudden death has a very high incidence, which could be explained by the development of complete a-v block, because of the impairment of the conduction system. Therefore, in those patients with bifascicular blocks (3 cases), the electrophysiological study may be useful in order to evaluate the opportunity to put on a permanent pace-maker, to prevent sudden death. 相似文献
57.
David I. Bernstein Derek A. Pullum Rhonda D. Cardin Fernando J. Bravo David A. Dixon Konstantin G. Kousoulas 《Vaccine》2019,37(1):61-68
Background
Although development of an HSV vaccine is a priority there is currently no vaccine available. The recent failure of subunit vaccines suggest that presentation of more antigens via a live attenuated vaccine may be required for protection. We therefore evaluated VC2, a live attenuated HSV vaccine, engineered to be unable to enter into neuronal axons.Methods
VC2 pathogenesis was first evaluated in guinea pigs following intravaginal inoculation. VC2 was then evaluated as a prophylactic and therapeutic vaccine and compared protection to a gD2 vaccine adjuvanted with MPL/Alum in the guinea pig model of genital HSV-2. The guinea pig model allows evaluation of acute and recurrent disease, as well as vaginal shedding acutely and during episodes of recurrent activation.Results
VC2 was significantly attenuated in guinea pigs compared to the wild type strain, 17syn+. It replicated poorly at the inoculation site, did not produce any genital disease and rarely infected the neural tissue. After prophylactic vaccination, the VC2 vaccine decreased the clinical severity of acute and recurrent HSV-2 disease and shedding and decreased the quantity of virus in the DRGs. When compared to gD2+MPL/Alum, VC2 was somewhat more effective especially as it relates to neural tissue infection. VC2 was not effective as a therapeutic vaccine.Conclusion
The live attenuated prophylactic HSV vaccine, VC2, was effective in the guinea pig model of genital HSV-2. Its decreased ability to infect neural tissues provides advantages over other live attenuated vaccines. 相似文献58.
59.
60.
Cholesterol-fed rabbits were used to test potential anti-atherosclerotic effects of diltiazem, a calcium antagonist of the benzothiazepine type. Two groups of 7 rabbits each were fed standard laboratory chow supplemented with 1% cholesterol. One group received a 60 mg sustained release diltiazem capsule twice a day and the other group received a placebo capsule twice a day. A third group of control animals were fed an unmodified basal diet under conditions exactly the same as the experimental groups. All groups were studied over a period of 16 weeks. The cholesterol-fed animals showed a marked increase in plasma total cholesterol which was not significantly different for the diltiazem and placebo groups. Plasma calcium levels, blood pressure, and heart rate were also unchanged from the control animals. In the diltiazem-treated animals, 47.5 +/- 10.5% of the aortae showed atherosclerotic lesions; the value for the placebo group was 43.1 +/- 8.1%. Similar results were obtained for the coronary arteries. These results show that diltiazem treatment in the doses employed in this study had no effect on the reduction of atherosclerosis in this animal model. 相似文献