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Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.  相似文献   
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Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.  相似文献   
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Background

Bone mineral density (BMD) has been found to improve after parathyroidectomy (PTX) in patients with primary hyperparathyroidism. There are few data on the effect of PTX on BMD in normocalcemic and normohormonal primary hyperparathyroidism.

Methods

A retrospective analysis of 92 primary hyperparathyroidism patients who underwent PTX between 2004 and 2012 with pre- and post-PTX dual-energy x-ray absorptiometry was performed. Within-person changes in BMD pre- and post-PTX were analyzed using log linear mixed models, stratified by biochemical status.

Results

Bone mineral density increased post-PTX in the whole cohort at the lumbar spine (+2.5%), femoral neck (+2.1%), and total hip (+1.9%) and decreased at the one-third radius (–0.9%). On comparison of BMD changes by profile, BMD increased in those with the typical profile at the lumbar spine (3.2%), femoral neck (2.9%), and total hip (2.9%) but declined at the one-third radius (–1.5%). In contrast, BMD improved only at the femoral neck (4.3%) in the normohormonal group and did not change at any site in the normocalcemic group. The typical group had a greater increase in BMD over time at the femoral neck and total hip compared with normocalcemic patients.

Conclusion

Our results indicate that the skeletal benefit of PTX was attenuated in normocalcemic and normohormonal patients, suggesting that skeletal changes after PTX may depend on biochemical profile.  相似文献   
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目的:比较雷贝拉唑三联疗法与兰索拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡的疗效。方法:将幽门螺杆菌阳性的消化性溃疡83例分为两组:治疗组(雷贝拉唑三联疗法组)41例,以雷贝拉唑10mg,阿莫西林1000mg及甲硝唑400mg每日2次口服,治疗1周后单独服用雷贝拉唑10mg,连服7d;对照组(兰索拉唑三联疗法组)42例:以兰索拉唑30mg,阿莫西林1000mg及甲硝唑400mg,每日2次口服,治疗1周后单独服用兰索拉唑30mg,连服7d。治疗期间每周门诊随诊,记录临床症状改善情况,用药结束1个月后复查胃镜并检测幽门螺杆菌结果。结果:治疗组和对照组1d的临床症状缓解率分别为80%、60%,差异有统计学意义(P<0.05);1周后症状缓解率均为98%。治疗组和对照组的溃疡愈合率分别为93%和76%,差异有统计学意义(P<0.05);治疗组和对照组的总有效率分别为98%和96%,差异无统计学意义(P>0.05)。治疗组和对照组的幽门螺杆菌根除率分别85%和81%,差异无统计学意义(P>0.05)。结论:两组方案均能有效治疗消化性溃疡和缓解临床症状,并能有效地根除幽门螺杆菌。但雷贝拉唑三联疗法在改善临床症状和促进溃疡愈合方面优于兰索拉唑三联疗法。  相似文献   
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Sir, Aminoglycoside-induced renal tubular dysfunction could be dividedinto Fanconi-like syndrome (FS) and Bartter-like syndrome (BS)[1]. The risk factors and mechanisms of tubular dysfunctionare little known. Here, we report a case of gentamicin-inducedFS, BS and distal renal tubular acidosis (RTA) and propose thepossible involvement of mitochondria. Case. A 66-year-old Chinese male was admitted because ofpneumonia.  相似文献   
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The spine, pelvic bones and long bones of the lower extremities are common sites for insufficiency fractures. Cases of sternum insufficiency fractures have been rarely reported in an elderly patient. Insufficiency fracture tends to occur in bones with decreased mechanical strength. It tends to occur in elderly patients, especially in postmenopausal women, with underlying diseases. We describe a case of sternum insufficiency fracture in a patient with rheumatoid arthritis and systemic lupus erythematosus on long-term corticosteroid therapy diagnosed in an emergency setting. Sternum insufficiency fracture is a rare cause of chest pain. This case serves to remind the emergency physician to remain vigilant for other noncardiac and nontraumatic causes of chest pain. If diagnosed accurately, these patients can be discharged and treated as outpatients.  相似文献   
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