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31.
Thrombocytosis is an important laboratory finding in rheumatoid arthritis (RA) and it has a correlation with disease activity.
Janus kinase 2 valin 617 phenylalanine (JAK2V617F) mutation has gained importance in the diagnosis of myeloproliferative diseases
recently. There is no published report in literature on the association between RA and JAK2V617F-positive essential thrombocythemia
(ET). In this report, we present a JAK2V617F-positive ET case that had RA. A 57-year-old male patient was diagnosed with RA
according to the criteria of American College of Rheumatology (ACR), whose complaint was of pain in the hands and morning
stiffness lasting for about 2 h. The patient was evaluated for thrombocytosis because he was in remission and suffering persistent
thrombocytosis under treatment. After excluding the causes of secondary thrombocytosis, bone marrow aspiration and biopsy
was performed. On peripheral blood and bone marrow PCR examination, the patient was detected to be JAK2V617F positive heterozygously
and diagnosed with ET. As a conclusion, mild–moderate thrombocytosis is frequent in RA; however, ET can be diagnosed by JAK2V617F
evaluation in peripheral blood in thrombocytosis, especially when platelet count is more than 1 million/ml and when persisting
thrombocytosis is detected in RA remission. 相似文献
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Bozkurt B Bolos M Deswal A Ather S Chan W Mann DL Carabello B 《Journal of cardiac failure》2012,18(3):183-193
BackgroundIt is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α1,β1,β2-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions.Methods and ResultsIn 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II–IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCFc). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCFc-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCFc relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months.ConclusionsDespite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance. 相似文献
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Mustafa Tugrul Goktas Ragip Ozgur Karaca Said Kalkisim Lokman Cevik Levent Kilic Ali Akdogan Melih O. Babaoglu Atilla Bozkurt Leif Bertilsson Umit Yasar 《Basic & clinical pharmacology & toxicology》2017,121(4):266-271
Behçet's disease (BD) is a systemic autoimmune disorder. Cytochrome P450 enzymes (CYPs) are responsible for various drug metabolism reactions as well as those of endogenous substances which may be associated with autoimmune disease susceptibility. Recently, we reported that in patients with BD, CYP2C9 seems to be down‐regulated due to inflammation. In the same Turkish patients with BD, we investigated whether also CYP2C19 activity is decreased. Lansoprazole (30 mg) was given as a probe drug to evaluate CYP2C19 activity in 59 patients with BD and 27 healthy control volunteers. An HPLC method was used to determine plasma lansoprazole and its metabolite, 5‐hydroxy lansoprazole, concentrations. The genotyping for CYP2C19 *2, *3 and *17 polymorphisms was made using PCR‐RFLP. The median lansoprazole/5‐hydroxy lansoprazole metabolic ratio (MR) in patients with BD was 2.6‐fold higher as compared to the healthy control group (p = 0.001, 22.6 (1.3–26) and 8.8 (0.5–140) as median and range, respectively). The CYP2C19*17*17 genotype frequency was found to be significantly less in the BD group as compared to the healthy controls (1.7% versus 14.8% in controls, p = 0.01). Additionally, colchicine treatment did not affect the CYP2C19 enzyme activity in six patients (p = 0.43). In conclusion, the patients with BD had lower CYP2C19 enzyme activity and lower frequency of the CYP2C19*17 allele as compared to those of the healthy controls. Further studies are warranted on the mechanisms underlying this relation. This study should also be applied to other autoimmune diseases similarly characterized by local or systemic inflammation. 相似文献
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The mammalian target of rapamycin (TOR) has been implicated in the control of different stressors, growth factors, nutrients and hormones, participating in the control of key cellular functions. Controlling this many pathways poses mTOR signalling as a potential new target in new treatment strategies for multiple cancer types. mTOR components could potentially mislocated in tumour cells, which could lead to activation of signalling pathway that should not be active. Therefore, we aimed to show localisation of mTOR signal proteins in testicular seminoma. Tumoural testicular tissues were obtained from 10 patients with unilateral classic seminoma undergoing to therapeutic orchidectomy and compared with control human testicular tissues. Upon immunohistochemical evaluation, we detected mTOR and p‐mTOR (serine 2448), P70S6K, p‐P70S6K, PKCalpha and p‐PKCalpha, CD36 and MAPLC3 proteins in the cytoplasm of Sertoli cells in the seminiferous tubules. We also showed cytoplasmic perinuclear staining in seminoma cells. This study demonstrated the interaction of mTOR signalling pathway and testicular seminoma by showing intense cytoplasmic mTOR pathway proteins immunoreactivity in the seminoma, for the first time in humans. Therefore, we suggested that mTOR signalling components could create new clinical targets for treatment of testicular seminoma patients and male infertility in the future. 相似文献
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