全文获取类型
收费全文 | 678篇 |
免费 | 47篇 |
国内免费 | 42篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 24篇 |
妇产科学 | 7篇 |
基础医学 | 77篇 |
口腔科学 | 14篇 |
临床医学 | 92篇 |
内科学 | 171篇 |
皮肤病学 | 7篇 |
神经病学 | 23篇 |
特种医学 | 196篇 |
外科学 | 19篇 |
综合类 | 12篇 |
一般理论 | 1篇 |
预防医学 | 31篇 |
眼科学 | 3篇 |
药学 | 29篇 |
中国医学 | 1篇 |
肿瘤学 | 54篇 |
出版年
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 11篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 14篇 |
2014年 | 10篇 |
2013年 | 16篇 |
2012年 | 7篇 |
2011年 | 12篇 |
2010年 | 16篇 |
2009年 | 22篇 |
2008年 | 16篇 |
2007年 | 40篇 |
2006年 | 20篇 |
2005年 | 22篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 10篇 |
2001年 | 7篇 |
2000年 | 4篇 |
1999年 | 9篇 |
1998年 | 35篇 |
1997年 | 33篇 |
1996年 | 40篇 |
1995年 | 31篇 |
1994年 | 47篇 |
1993年 | 28篇 |
1992年 | 9篇 |
1991年 | 11篇 |
1990年 | 13篇 |
1989年 | 38篇 |
1988年 | 39篇 |
1987年 | 36篇 |
1986年 | 25篇 |
1985年 | 19篇 |
1984年 | 16篇 |
1983年 | 12篇 |
1982年 | 13篇 |
1981年 | 7篇 |
1980年 | 9篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 8篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1972年 | 2篇 |
1966年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有767条查询结果,搜索用时 15 毫秒
21.
22.
Zielinsky A; Hirsh J; Straumanis G; Carter CJ; Gent M; Sackett DL; Hull R; Kelton JG; Powers P; Turpie AG 《Blood》1982,59(2):346-350
We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice. 相似文献
23.
Jacqueline AM Smith DL Patil OT Daniels Y-S Ding J-D Gallezot S Henry KHS Kim S Kshirsagar WJ Martin GP Obedencio E Stangeland PR Tsuruda W Williams RE Carson ST Patil 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(2)
Background:
Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.Methods:
We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.Results:
TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [11C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [11C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.Conclusions:
These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation. 相似文献24.
Dziennis S; Van Etten RA; Pahl HL; Morris DL; Rothstein TL; Blosch CM; Perlmutter RM; Tenen DG 《Blood》1995,85(2):319-329
CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells. 相似文献
25.
Cathleen S. Colón-Emeric Carl F. Pieper Courtney H. Van Houtven Janet M. Grubber Kenneth W. Lyles Joanne Lafleur Robert A. Adler 《Mayo Clinic proceedings. Mayo Clinic》2018,93(12):1749-1759
Objective
To determine the association between dual-energy x-ray absorptiometry (DXA) testing for osteoporosis and subsequent fractures in US male veterans without a previous fracture.Patients and Methods
This is a propensity score–matched observational study using Centers for Medicare and Medicaid Services and Veterans Affairs (VA) data from January 1, 2000, through December 31, 2010, with a mean follow-up time of 4.7 years (range, 0-10 years). Men receiving VA primary care aged 65 to 99 years without a previous fracture (N=2,539,812) were included. Men undergoing DXA testing were propensity score matched with untested controls in a 1:3 ratio, indicating the probability of DXA testing within the next year. Time to first clinical fracture was the primary outcome. Comorbidities, demographic characteristics, medications, DXA results, and osteoporosis treatment were defined using administrative data and natural language processing. A landmark analysis contingent on surviving to 12 months after screening was completed, accounting for competing risk of mortality.Results
During follow-up of 153,311 men tested by DXA and 390,158 controls, 56,083 (10.3%) had sustained a fracture and 111,774 (20.6%) died. Overall, DXA testing was not associated with a decrease in fractures; conclusions are limited by unmeasured confounders and low medication initiation and adherence in those meeting treatment thresholds (12% of follow-up time). In contrast, DXA testing in prespecified subgroups was associated with a lower risk of fracture in comparison to the overall population who underwent DXA testing: androgen deprivation therapy (hazard ratio [HR], 0.77; 95% CI, 0.66-0.89), glucocorticoids (HR, 0.77; 95% CI, 0.72-0.84), age 80 years and older (HR, 0.85; 0.81-0.90), 1 or more VA guideline risk factors (HR, 0.91; 95% CI, 0.87-0.95), and high Fracture Risk Assessment Tool using body mass index score (HR, 0.90; 95% CI, 0.86-0.95).Conclusion
Current VA DXA testing practices are ineffective overall; interventions to improve treatment adherence are needed. Targeted DXA testing in higher-risk men was associated with a lower fracture risk. 相似文献26.
Cold storage of platelets in platelet additive solution: an in vitro comparison of two Food and Drug Administration–approved collection and storage systems
下载免费PDF全文
![点击此处可从《Transfusion》网站下载免费的PDF全文](/ch/ext_images/free.gif)
27.
Treatment of liver failure in rats with end-stage cirrhosis by transplantation of immortalized hepatocytes 总被引:12,自引:0,他引:12
Cai J Ito M Nagata H Westerman KA Lafleur D Chowdhury JR Leboulch P Fox IJ 《Hepatology (Baltimore, Md.)》2002,36(2):386-394
The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, 35 immortalized rat hepatocyte clones were developed by transduction with the gene encoding the simian virus 40 T antigen (SV40Tag). The SV40Tag sequence and a suicide gene, herpes simplex virus thymidine kinase (HSV-tk), were flanked by loxP sequences so that they could be excised by Cre/lox recombination. When transplanted into the spleens of portacaval-shunted rats, 3 of the 35 immortalized hepatocyte clones prevented the development of hyperammonemia-induced hepatic encephalopathy. The protection was reversed by treatment with ganciclovir, which kills HSV-tk-expressing cells. Transplantation of alginate-encapsulated, immortalized hepatocytes into the spleens of cirrhotic rats resulted in significant improvement in prothrombin time, serum albumin and bilirubin levels, hepatic encephalopathy score, and duration of survival. The metabolic support provided by the immortalized cells equaled that observed after transplantation of primary rat hepatocytes. In conclusion, immortalized hepatocytes can function as well as primary hepatocytes following transplantation and can be engineered to contain safeguards that could make them clinically useful. Further investigation is warranted regarding the mechanisms of loss of mass or function of the transplanted hepatocytes over time and how the relatively few engrafted hepatocytes can ameliorate liver decompensation in cirrhosis. 相似文献
28.
29.
Georgina L Ryland Sally M Hunter Maria A Doyle Simone M Rowley Michael Christie Prue E Allan David DL Bowtell Australian Ovarian Cancer Study Group Ian G Campbell 《The Journal of pathology》2013,229(3):469-476
Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under‐described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild‐type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
30.
VY Kong B Sartorius DL Clarke 《Annals of the Royal College of Surgeons of England》2015,97(5):390-395
IntroductionAcute appendicitis in the developing world has a markedly different disease profile to that in the developed world.MethodsA retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis.ResultsA total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%.Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was £2,060,972.ConclusionsAcute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system. 相似文献