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41.
Endotoxin promotes synergistic lethality during concurrent Escherichia coli and Candida albicans infection. 总被引:4,自引:0,他引:4
Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens. To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E. coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed. E. coli (2 x 10(7) colony-forming units (CFU)) plus C. albicans (6 x 10(7) CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E. coli or C. albicans alone (20 and 3%, respectively, P less than 0.01). Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P less than 0.05), endotoxemia (3653 +/- 3187 versus 2 +/- 2 endotoxin units (EU), P less than 0.01), and bacteremia (4.2 +/- 2.3 versus 1.1 +/- 2.1 log(CFU/ml), P less than 0.01) compared to animals receiving saline alone. In a separate series of experiments, purified E. coli 0111:B4 LPS was administered in place of viable E. coli. The simultaneous injection of 200 micrograms E. coli LPS and C. albicans (6 x 10(7) CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E. coli 0111:B4 LPS or C. albicans alone (21 and 3% respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
42.
OBJECTIVE--To assess current strategies used to investigate and manage acute atrial fibrillation in hospital. DESIGN--Prospective survey of all acute admissions over 6 months. SETTING--District general hospital serving a population of 230,000 in north east Glasgow. SUBJECTS--2686 patients admitted as emergency cases over 6 months. RESULTS--Of the 2686 patients, 170 (age range 38-95, mean (SD) 73.5 (10.6) years; 70 men (41%) and 100 women (59%)) were admitted with atrial fibrillation. The principal underlying medical conditions were ischaemic heart disease in 79 (46.5%), rheumatic heart disease in 26 (15.3%), and thyroid disease in six (3.5%). Cardiac failure was present on admission in 61 (36%), cerebrovascular events in 23 (14%), and myocardial infarction in 17 (10%). Of those with a history of atrial fibrillation (102 (60%) including 10 with paroxysmal atrial fibrillation) treatment on admission included digoxin in 71 (70%), warfarin in 20 (20%), and aspirin in 17 (17%); the aspirin was predominantly given for concomitant vascular disease. The mean (SD) inpatient stay was 16 days (19.7) (range 1-154) largely due to the patients with stroke. Thyroid function tests were performed in only 63% and echocardiography in 33%. Overall, the rate of introduction of anticoagulation (seven patients) and attempted cardioversion (21 patient: 19 pharmacological and two electrical) was surprisingly low. Only 49 patients (34% of those not on warfarin) had contraindications to anticoagulation: these included peptic ulcer or gastrointestinal bleeding in 18 (12%), dementia in eight (6%), chronic renal failure or dialysis in eight (6%), and alcohol excess in four (3%). CONCLUSION--Standard investigations were inadequately used in patients with atrial fibrillation and there was a reluctance to perform cardioversion or to start anticoagulant treatment. 相似文献
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Kenneth W. Locke Robert W. Dunn John W. Hubbard Cheri L. Vanselous Michael Cornfeldt Stuart Fielding Joseph T. Strupczewski 《Drug development research》1990,19(3):239-256
HP 818 (1-benzoyl-6-fluoro-3-(1-methyl-4-piperidinyl)-1H-indazole) exhibits the profile of a potent nonnarcotic analgesic with neuroleptic properties. HP 818 blocks the effects of chemical (phenylquinone), pressure (tail clip), and radiant heat (tail flick) painful stimuli in mice (ED50 values of 0.3, 1.2, and 4.1 mg/kg s.c., respectively). This compound displays antinociceptive activity by the subcutaneous, oral, and intravenous routes of administration. It is also effective in the shock titration assay in squirrel monkeys and in a model of surgically induced pain. The rank order of potency of HP 818 and several other standard compounds in these tests for analgesia was Innovar > fentanyl > HP 818 > codeine > droperidol. In addition to its antinociceptive effects, HP 818 possesses neuroleptic properties. It is active in the climbing mouse, pole climb avoidance, and intracranial self-stimulation assays (ED50 values of 1.8, 1.7, and 2.5 mg/kg i.p., respectively). Moreover, HP 818 inhibits amphetamine- and apomorphine-induced stereotypy, indicative of D2-dopaminergic blocking properties. HP 818, unlike typical neuroleptic agents, does not induce supersensitivity to the effects of apomorphine when administered chronically in mice. In contrast to the clinical standard neuroleptanalgesic Innovar, HP 818 (1.0–3.0 mg/kg i.v.) produces no significant cardiovascular or respiratory changes in the anesthetized dog. Thus, HP 818 is potentially an effective presurgical medication due to its nonnarcotic analgesic activity and sedative neuroleptic effects, along with its lack of limiting cardiorespiratory side effects. 相似文献
46.
M D Schulman C T Evensen C W Runyan L R Cohen K A Dunn 《The Journal of rural health》1997,13(4):295-305
Children who work in agriculture suffer more than 23,000 injuries and 300 fatalities on American farms every year. Using survey data collected from a random sample of working teens (ages 14 to 17) in North Carolina, the authors analyze the farm-based hazard exposure and injury experiences of teens who work on farms. The group of farmworking teens (N = 141) is 72 percent male, has a mean age of 16.6 years, and is, on average, in the 10th grade. The data show that teens working on farms in North Carolina are exposed to significant safety hazards throughout their farmworking careers. A majority of the respondents in this group of farmworkers reported exposure to tractors, large animals, all-terrain vehicles, farm trucks, and rotary mowers, and more than one-third reported exposure to pesticides and tobacco harvesters. Common reported injuries include insect stings, cuts, burns, and falls. The researchers find that gender, age, and farmwork experiences are related to variations in types of hazards to which teens are exposed and in the types of injuries they suffer. These variables also are related to the overall complexity of the teens' farmwork experiences and the burden of injury endured by teens. 相似文献
47.
The impact of technology and improved perioperative management upon survival from carcinoma of the pancreas 总被引:1,自引:0,他引:1
E Dunn 《Surgery, gynecology & obstetrics》1987,164(3):237-244
A community hospital experience of 238 instances of carcinoma of the pancreas during a 23 year period has been reviewed to see if there has been any change in survival, hospital stay, morbidity and operative strategy during the two decades included in this study as a result of improved diagnostic modalities and perioperative management. The results of this review indicate an increasing incidence of carcinoma of the pancreas in the second half of the study but also document a large number of patients whose diagnosis has been unsuspected until autopsy. The mortality for palliative bypass procedures dropped significantly in the second half of the study and provided a mean survival time of 7.6 months for this group of patients, approximately twice that of patients explored without palliation. Resectional procedures showed a very significant drop in mortality rate in the second half of the study and were used more extensively. Mean survival time of patients undergoing resectional procedures was 18.3 months with two prolonged survivors out of 22 patients. Significant operative morbidity remains a major problem and the chief cause of protracted postoperative stay and did not diminish in the second half of this study. Complications were primarily technical in nature. With this in mind, consideration should be given to concentrating the experience in pancreatic resectional operations in the hands of a limited number of surgeons within any given community. 相似文献
48.
Obstruction of a Bjork-Shiley mitral valve prosthesis occurred in a 41 year old woman due to pannus tissue growing over the valve and impairing disc opening. The unusual intermittent nature of the obstruction was clearly demonstrated by Doppler ultrasound. The pannus was excised and the valve prosthesis replaced successfully with a Carpentier-Edwards xenograft. 相似文献
49.
Correlation between serological and mucosal inflammatory responses to Helicobacter pylori. 下载免费PDF全文
G I Pérez-Pérez W R Brown T L Cover B E Dunn P Cao M J Blaser 《Clinical and Vaccine Immunology : CVI》1994,1(3):325-329
In 82 patients who underwent gastroduodenoscopy, acute and chronic gastric mucosal inflammation was scored for severity, and systemic humoral immune responses to Helicobacter pylori antigens were assessed by enzyme-linked immunosorbent assays. On the basis of culture, gastric histology, and serologic evaluation, 33 patients were classified as H. pylori infected and 36 were classified as uninfected. Thirteen patients had negative cultures and stains but were seropositive and were analyzed separately from the other two groups. Specific serum immunoglobulin G (IgG) subclass responses to H. pylori whole-cell antigens and specific IgG responses to the 54-kDa heat shock protein homolog (Hp54K) and vacuolating cytotoxin were significantly greater in infected than in uninfected patients as were specific IgA responses to whole-cell antigens and cytotoxin (P < 0.001). Among the H. pylori-infected persons, serum IgG responses to Hp54K and to the vacuolating cytotoxin were correlated with acute mucosal inflammatory scores. In contrast, serum IgA responses to whole-cell sonicate and to vacuolating cytotoxin were inversely related to chronic inflammatory scores. By multivariant regression analysis, only specific serum IgG responses to Hp54K correlated with severity of inflammation (both acute and chronic; P < 0.001); these responses may be markers of inflammation or these antibodies could play a direct role in the pathogenesis of H. pylori-induced inflammation. 相似文献
50.
J.P. Neoptolemos M. G.T. Raraty P. Ghaneh H. Hickey D.D. Stocken J. A. Dunn H. Friess M.W. Büchler 《Der Chirurg》2003,74(3):191-201
Recent advances have been made in the treatment of pancreas cancer. Specialized pancreas centres have reported an increasing rate of resections with reduced postoperative mortality. On account of the highly aggressive nature of pancreas cancer, there is a great challenge in identifying effective therapy concepts for advanced stages of the cancer as well as for the development of resection-associated measures. As large-scale, randomised, controlled studies are lacking, the additive therapy concepts after resection do not have a sufficiently scientific basis. The ESPAC-1 study, which included 600 patients, surpassed all previous studies on adjuvant therapy for pancreas cancer. This study has shown,for example, that the most promising adjuvant chemotherapy with 5-fluorouracil and folic acid leads to an equal if not better result than the multimodal regimen. This regimen can be superseded with the use of Gemcitabine, which will be evaluated in the ESPAC-3 study that includes 990 patients from various European countries including Germany, as well as from Canada and Australia. Participation in the large, phase-3 study therefore plays a key role in the continued development of the management of pancreas cancer. 相似文献