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31.
为研究Mpl受体介导的HEL细胞电子传递反应的变化,建立了用细胞电极测定HEL细胞电子传递的电化学方法。结果发现,当TPO-Mpl作用后数分钟可以观察到一个向上的“”形氧化电位,TPO-Mpl的最大作用出现在5分钟内,TPO-Mpl的解离在二者作用后60分钟趋向明显,240分钟后完全解离。Scatchard分析说明HEL细胞表面有两种Mpl受体亲和力(K_1=1.8 pmol/L,K_2=1.11nmol/L)。结果提示,TPO与Mpl受体结合迅速,解离缓慢,HEL细胞上存在两种亲和力的Mpl受体。该方法灵敏、方便,可以连续观察,需要细胞少(1.0×10~4细胞)。 相似文献
32.
MAY CI VAN SCHALKWYK NASON MAANI JONATHAN COHEN MARTIN MCKEE MARK PETTICREW 《The Milbank quarterly》2021,99(2):467
Policy Points
- Despite the pandemic''s ongoing devastating impacts, it also offers the opportunity and lessons for building a better, fairer, and sustainable world.
- Transformational change will require new ways of working, challenging powerful individuals and industries who worsened the crisis, will act to exploit it for personal gain, and will work to ensure that the future aligns with their interests.
- A flourishing world needs strong and equitable structures and systems, including strengthened democratic, research, and educational institutions, supported by ideas and discourses that are free of opaque and conflicted influence and that challenge the status quo and inequitable distribution of power.
33.
目的:评价鼻内窥镜下筛窦切除术治疗视神经炎的疗效。方法:对4例视神经炎患者行鼻内窥镜下筛窦切除术。结果:显效2例,有效2例。鼻塞,眼胀,头痛症状缓解。结论:对合并有筛窦炎的视神经炎患者,在保守治疗无效或治疗后有反复时,及时行鼻内窥镜下筛窦切除术有效率高,且安全、可靠。 相似文献
34.
DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model 下载免费PDF全文
Berul CI Maguire CT Aronovitz MJ Greenwood J Miller C Gehrmann J Housman D Mendelsohn ME Reddy S 《The Journal of clinical investigation》1999,103(4):R1-R7
Myotonic dystrophy (DM) is the most common form of muscular dystrophy and is caused by expansion of a CTG trinucleotide repeat on human chromosome 19. Patients with DM develop atrioventricular conduction disturbances, the principal cardiac manifestation of this disease. The etiology of the pathophysiological changes observed in DM has yet to be resolved. Haploinsufficiency of myotonic dystrophy protein kinase (DMPK), DM locus-associated homeodomain protein (DMAHP) and/or titration of RNA-binding proteins by expanded CUG sequences have been hypothesized to underlie the multi-system defects observed in DM. Using an in vivo murine electrophysiology study, we show that cardiac conduction is exquisitely sensitive to DMPK gene dosage. DMPK-/- mice develop cardiac conduction defects which include first-, second-, and third-degree atrioventricular (A-V) block. Our results demonstrate that the A-V node and the His-Purkinje regions of the conduction system are specifically compromised by DMPK loss. Importantly, DMPK+/- mice develop first-degree heart block, a conduction defect strikingly similar to that observed in DM patients. These results demonstrate that DMPK dosage is a critical element modulating cardiac conduction integrity and conclusively link haploinsufficiency of DMPK with cardiac disease in myotonic dystrophy. 相似文献
35.
Warunee Dansithong Cordula M. Wolf Partha Sarkar Sharan Paul Andy Chiang Ian Holt Glenn E. Morris Dorothy Branco Megan C. Sherwood Lucio Comai Charles I. Berul Sita Reddy 《PLoS Clinical Trials》2008,3(12)
The genetic basis of myotonic dystrophy type I (DM1) is the expansion of a CTG tract located in the 3′ untranslated region of DMPK. Expression of mutant RNAs encoding expanded CUG repeats plays a central role in the development of cardiac disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates, yet the relative significance of such aggregates in eliciting DM1 pathology is unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed and analyzed mice with cardiac-specific expression of a beta-galactosidase cassette in which a (CTG)400 repeat tract was positioned 3′ of the termination codon and 5′ of the bovine growth hormone polyadenylation signal. In these animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant RNA splicing. Abnormal splicing results from the functional inactivation of MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm results both in Mbnl1 sequestration and in approximately a two fold increase in both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes RNA splice defects were not observed and functional analysis revealed only subtle cardiac dysfunction, characterized by conduction defects that primarily manifest under anesthesia. Using a human myoblast culture system we show that this transgene, when expressed at similar levels to a second transgene, which encodes expanded CTG tracts and facilitates both nuclear focus formation and aberrant splicing, does not elicit aberrant splicing. Thus the lack of toxicity of cytoplasmic CUG foci does not appear to be a consequence of low expression levels. Our results therefore demonstrate that the cellular location of CUG RNA aggregates is an important variable that influences toxicity and support the hypothesis that small molecules that increase the rate of transport of the mutant DMPK RNA from the nucleus into the cytoplasm may significantly improve DM1 pathology. 相似文献
36.
Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and ryanodine receptors, causing catecholaminergic polymorphic ventricular tachycardia 总被引:7,自引:1,他引:7 下载免费PDF全文
Song L Alcalai R Arad M Wolf CM Toka O Conner DA Berul CI Eldar M Seidman CE Seidman JG 《The Journal of clinical investigation》2007,117(7):1814-1823
37.
目的:探讨草分支杆菌注射液联合苄星青霉素在早期梅毒治疗中的作用。方法:将80例早期梅毒患者分为治疗组(草分支杆菌注射液联合苄星青霉素)和对照组(单用苄星青霉素),观察时间6个月。结果:治疗3、6个月时治疗组快速血浆反应素试验(RPR)几何平均滴度低于对照组(P<0.05),治疗6个月治疗组RPR阴转率为40%,对照组为21.2%,两者差异有统计学意义(P<0.05)。结论:草分支杆菌注射液辅助治疗早期梅毒可以增强苄星青霉素驱梅的疗效。 相似文献
38.
目的:探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)并肺动脉高压(pulmonary arterial hypertension,PAH)患者的临床特点及发病机制,方法:37例经彩色多普勒超声心动图诊断明确、资料完整的SLE合并PAH患者,对其临床症状、实验室指标、超声心动图特点、SLEDAI积分进行回顺性分析.结果:本组患者抗nRNP阳性、抗心磷脂抗体IgG异常、浆膜炎、SLEDAI评分和肺间质病变出现率均增高,与PAH的发生率成正相关结论:SLE是自身免疫性疾病中合并PAH较常见的疾病,对于出现雷诺现象、皮肤血管炎、抗nRNP阳性、抗心磷脂抗体IgG阳性以及浆膜炎和肺间质病变的SLE患者应警惕PAH的可能,彩色多普勒超声心动图及相关检查有利于早期诊断. 相似文献
39.
40.
目的 探讨抗程序化细胞死亡基因5(PDCD5)抗体在类风湿关节炎(RA)中的意义.方法 采用酶联免疫吸附法(ELISA)对55例RA 患者和44例健康对照者(NC)外周血清中抗PDCD5抗体的水平进行检测,并与RA患者相关临床资料、实验室指标及影像学资料进行统计学分析.结果 55例RA患者和44例NC外周血清中抗PDCD5抗体的水平分别为(18.06±4.70)μg/L,(13.62±4.35)μg/L,阳性率分别为18.2%(10/55),4.5%(2/44),二者在抗体水平和阳性率上差异有统计学意义(P<0.05).抗PDCD5抗体阳性组Sharp评分,类风湿因子(RF)和抗环瓜氨酸肽(CCP)抗体水平明显高于抗PDCD5抗体阴性组,抗PDCD5抗体与抗CCP抗体呈正相关(r=0.374,P=0.01,2-tailed).结论 抗PDCD5抗体与RA密切相关,且抗体阳性患者易出现骨侵蚀,有望成为诊断早期RA的实验室指标之一. 相似文献