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The first 150 words of the full text of this article appear below. Key points Coronary artery disease accounts for >30% ofdeaths in Western society. The diagnosis of myocardial infarctionshould be qualified by size, causation and time from occurrence. Mortalityis reduced by immediate or primary percutaneouscoronary intervention or thrombolysis within the first 24 hof onset of ST-segment elevation myocardial infarction. Strategiesto reduce platelet activation (glycoprotein IIb/IIIa receptorantagonists, or clopidogrel) are now recommended in the treatmentof high-risk non-ST-segment myocardial infarction/unstable angina. Elevatedserum troponins may be the result of non-ischaemic myocardialdamage, especially in critical illness.
Pathophysiology
Changes in the definition of terms relating to the diagnosisof myocardial infarction (MI) have evolved by better understandingof the pathophysiology culminating in the new term of acutecoronary syndrome (ACS). Figure 1 illustrates the processesthat occur in the development of an acute coronary event. 相似文献
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Laurent P. Rivory Michael S. Roberts Susan M. Pond 《Journal of pharmacokinetics and pharmacodynamics》1992,20(1):19-61
An assumption of previous models of hepatic elimination is that there is negligible axial diffusion in the liver. We show, by construction of a stochastic model and analysis of published data, that compounds which are readily diffusible and partitioned into hepatocytes may undergo axial tissue diffusion. The compounds most likely to be affected by axial tissue diffusion are the lipophilic drugs for which the cell membranes provide little resistance and which are highly extracted, thereby creating steep concentration gradients along the sinusoid at steady state. This phenomenon greatly modifies the availability of the compound under conditions of altered hepatic blood flow and protein binding. For moderately diffusible compounds, these relationships are similar to those predicted by the simplistic venous-equilibrium model. Hence, the paradoxical ability of the venous-equilibrium model to describe the steady-state kinetics of lipophilic drugs such as lidocaine, meperidine, and propranolol may be finally resolved. The effects of axial tissue diffusion and vascular dispersion on hepatic availability of drugs are compared. Vascular dispersion is of major importance to the availability of poorly diffusible compounds, whereas axial tissue diffusion becomes increasingly dominant for highly diffusive and partitioned substances.This study was supported by the National Health and Medical Research Council of Australia. 相似文献
4.
Zhen-yu Wu Laurent P. Rivory Michael S. Roberts 《Journal of pharmacokinetics and pharmacodynamics》1993,21(6):653-688
Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analyses of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV
2
) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.We acknowledge the support of the National Heart Foundation (Queensland) and the Mayne Bequest Foundation. This study was conducted while the investigator (Z.Y. Wu) was in receipt of a WHO Research Training Grant. Professor M. S. Roberts also acknowledges the support of the Queensland and Northern New South Wales Lions Kidney & Medical Research Foundation. 相似文献
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J Bousquet J P Rivory M Maheut F B Michel C Mion 《The Journal of allergy and clinical immunology》1989,83(4):825-828
Pruritus is a common symptom among patients undergoing long-term hemodialysis. The effect of nicergoline, an ergoline, on pruritus was studied in products released during dialysis. In a first experiment series, 20 age-matched normal individuals, 25 patients receiving hemodialysis without pruritus, and 15 patients receiving hemodialysis with pruritus had intradermal tests with 500 micrograms of papaverine. All patients with pruritus had a small papaverine skin test response, and mean values were significantly (p less than 0.0001, Mann-Whitney U test) smaller in patients with pruritus. All patients with pruritus entered in a crossover, double-blind trial with nicergoline. In a first period of six dialyses, they received either nicergoline (daily oral dose, 30 mg, and intravenous dose during dialyses, 5 mg) or placebo. In the second period of six dialyses, patients received the crossover treatment. Nicergoline was effective in 13/15 patients, eight of these patients having a complete remission of pruritus. When nicergoline was stopped, patients relapsed within 24 to 48 hours. All patients who improved during the trial were then treated with a daily dose of 30 mg of nicergoline for 6 months. Seven patients had a complete remission, five had moderate symptoms, and one patient relapsed. This study demonstrated that some hemodialyzed patients with pruritus of unknown etiology had improvement with nicergoline. 相似文献
7.
Irinotecan (CPT-11) is an anticancer drug that occasionally produces acute cholinergic side effects. Preliminary findings suggest that these are mediated through the inhibition of acetylcholinesterase (AChE). In this study, the inhibition of various AChEs by CPT-11 was studied. The lactone form of CPT-11 resulted in apparent noncompetitive inhibition of electric eel and both human recombinant and erythrocyte AChE with K(i) values of 0.065, 0.19, and 0.29 microM, respectively. The carboxylate form of CPT-11 was approximately 10 times less potent. Apparent noncompetitive inhibition of AChE may arise through several mechanisms, and those relevant to CPT-11 were identified from key experimental findings. First, the inhibition by CPT-11 was found to be instantly reversible in dilution studies. Second, incubation of the enzyme with CPT-11 before the introduction of neostigmine protected the enzyme from inactivation. Third, regeneration of the active enzyme after preincubation with neostigmine was totally suppressed by the addition of 2 microM CPT-11, indicating that CPT-11 is a potent inhibitor of decarbamoylation and, by inference, deacylation. Additional experiments with tacrine revealed functional differences between these two inhibitors. Also, preliminary molecular modeling of the interaction between AChE and CPT-11 indicated that the latter does not bind at the same site as tacrine. Displacement studies with the peripheral site-specific ligand, propidium, confirmed that CPT-11 binds at this site. The rapid reversibility of the inhibition of AChE by CPT-11 and the lower activity of the carboxylate form are likely reasons for the transient nature of the cholinergic toxicity observed clinically. 相似文献
8.
Yanfang Li Menda LP Qiuliang WU Fuyuan Liu Jundong Li Jinglin Zou Yongwen Huang 《中国肿瘤临床(英文版)》2004,1(3):180-184
Objective Ovarian dysgerminoma is an uncommon ovarian malignancy, Its clinicai features are special and there are many factors affecting
its prognosis. If treated properly, the patient can be cured. Otherwise it may endanger the patient’s life. The aim of this
study is to investigate the clinical features and factors related to prognosis of ovarian dysgerminoma.
Methods Data from 57 patients with pure ovarian dysgerminoma were analyzed retrospectively. The patients were admitted to the Cancer
Center, Sun Yat-sen University from January 1.1964 to December 31, 2000.
Results The main clinical features were abdominal mass (56.1% ), abdominal pain (21.1% ), abdominal swelling (17.5%.), vaginal bleeding
(5.3% )and genital tract abnormalities (5.3%). Twenty-six patients had stage I diseases, 8 stage II.9 stage III.1 stage IV
and 13 recurrent and persistent diseases. The uterus was involved in 41.2% of patients with stage II -III diseases. Combined
modality was given to 52 cases and a single-method treatment to 5 cases. The total overall 5 and 10-year survival rates for
stages I-IV was 80.1 % and 70.0% respectively. The 5-year survival rate for stage I was 100%, stage II 55.2%. stage III 55.6%
and stage IV 0%; for recurrent and persistent diseases, 72.7%. The stage I group of 12 patients. received adnexectomy and
14 patients underwent hysterectomy and adnexa removal. There was no significant difference between the 5 and 10-year survival
rates (all 100%). Of the 23 patients in the stage I group to whom oniy chemotherapy was given after operation, 19 cases received
3 or more courses and were well without recurrence; 4 patients received only one course and one of them recurred 21 months
after the operation. In the group of stages II and III cases, the 5-year survival rate was 86.7% for those whose chemotherapy
courses were 3≥ 4 and 25.0% for patients who received less than 4 courses of chemotherapy (P<0.05).
Conclusions The prognosis of ovarian dysgerminoma is closely related to the disease stage and treatment modality. A fertility-preserving
operation can be considered in early -staged patients, but caution needs to be exercised in the middle to late staged cases.
Good results can be achieved with an operation-based combined modality in recurrent patients. 相似文献
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