全文获取类型
收费全文 | 1411篇 |
免费 | 109篇 |
国内免费 | 66篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 52篇 |
妇产科学 | 17篇 |
基础医学 | 157篇 |
口腔科学 | 1篇 |
临床医学 | 184篇 |
内科学 | 430篇 |
皮肤病学 | 3篇 |
神经病学 | 10篇 |
特种医学 | 14篇 |
外科学 | 155篇 |
综合类 | 96篇 |
现状与发展 | 1篇 |
预防医学 | 235篇 |
眼科学 | 3篇 |
药学 | 197篇 |
中国医学 | 10篇 |
肿瘤学 | 17篇 |
出版年
2023年 | 22篇 |
2022年 | 28篇 |
2021年 | 68篇 |
2020年 | 68篇 |
2019年 | 52篇 |
2018年 | 61篇 |
2017年 | 57篇 |
2016年 | 56篇 |
2015年 | 70篇 |
2014年 | 152篇 |
2013年 | 201篇 |
2012年 | 85篇 |
2011年 | 100篇 |
2010年 | 82篇 |
2009年 | 75篇 |
2008年 | 71篇 |
2007年 | 52篇 |
2006年 | 40篇 |
2005年 | 18篇 |
2004年 | 30篇 |
2003年 | 20篇 |
2002年 | 16篇 |
2001年 | 23篇 |
2000年 | 11篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 15篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 12篇 |
1993年 | 13篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有1586条查询结果,搜索用时 26 毫秒
61.
Lucas F Soveral Gabriela G Korczaguin Pedro S Schmidt Isabel S Nunes Camilo Fernandes Carlos R Z rate-Blad s 《World journal of gastroenterology : WJG》2022,28(33):4762-4772
Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT. 相似文献
62.
We recently published our findings indicating that anti-TcdB antibodies were effective as treatment for C. difficile infection, but that anti-TcdA actually worsened prognosis in the gnotobiotic piglet model. To further investigate the roles of the two toxins, we administered purified toxins separately or together, systemically, to piglets and found that both toxins, either alone or together, are able to elicit severe lesions systemically and are also able to cross into the gut lumen and cause large intestinal lesions typical of infection. We also found that anti-TcdA administered before systemic challenge with TcdA again did not protect from development of disease, but, in this case, did not appear to worsen prognosis. Further work is still needed, but these findings add to the growing knowledge regarding the roles of the C. difficile toxins. 相似文献
63.
Stephen T. Cartman John T. HeapSarah A. Kuehne Alan CockayneNigel P. Minton 《International journal of medical microbiology : IJMM》2010,300(6):387-395
The impact of Clostridium difficile-associated disease (CDAD) in healthcare settings throughout the developed world is considerable in terms of mortality, morbidity, and disease management. The incidence of CDAD has risen dramatically since the turn of this century, concomitant with the emergence of so-called hypervirulent strains which are thought to cause a more severe disease, higher relapse rates, and increased mortality. Pre-eminent amongst hypervirulent strains are those belonging to ribotype 027, which were first reported in Canada in 2003 and shortly thereafter in the UK. Since its arrival in Europe, it has spread rapidly and has now been reported in 16 member states and Switzerland. The physiological factors responsible for the rapid emergence of hypervirulent C. difficile strains remain unclear. It is known that they produce a binary toxin (CDT) in addition to toxins A and B, that they are resistant to fluoroquinolones due to mutations in gyrA, and that they are resistant to erythromycin. Representative strains have been suggested to produce more toxin A and B in the ‘laboratory flask’ (most likely due to a frameshift mutation in the repressor gene tcdC), to be more prolific in terms of spore formation, and also exhibit increased adherence to human intestinal epithelial cells due to altered surface proteins. However, the contribution of these and other as yet unidentified factors to the rapid spread of certain C. difficile variants (e.g., ribotypes 027 and 078) remains unclear at present. The advent of ClosTron technology means that it is now possible to construct genetically stable isogenic mutants of C. difficile and carry out reverse genetic studies to elucidate the role of specific gene loci in causing disease. The identification of virulence factors using this approach should help lead to the rational development of therapeutic countermeasures against CDAD. 相似文献
64.
目的 以rakicidin B1为起始原料,经2步反应合成得到4个全新结构的rakicidin B1衍生物,并对其进行生物学活性研究,以期获得低细胞毒、高效抗艰难梭菌活性的化合物。方法 课题组前期首次发现rakicidin B1具有较强的抗艰难梭菌活性,在其结构基础上进行修饰和优化,通过氨基甲酸酯连接基团引入含氮杂环,设计合成得到4个全新目标化合物。所有化合物结构经高分辩质谱和核磁确证,并经抗艰难梭菌活性测试和细胞毒性活性测试。结果 在合成的4个化合物中,有3个化合物具有与先导化合物更强或相当的抗艰难梭菌活性;同时,MTT测试结果表明,3个化合物的细胞毒性降低,以3b的细胞毒性降低最多。结论 通过对rakicidin B1母核结构进行修饰和优化,获得全新结构的rakicidin B1衍生物并对其进行抗菌和细胞毒活性筛选。其中,化合物3b保留潜在抗艰难梭菌活性且细胞毒性降低最多,作为全新结构类型的抗艰难梭菌活性化合物,有潜在的开发价值。 相似文献
65.
目的检测艰难梭菌毒素B(TcdB)对结肠癌SW480细胞增殖与凋亡的影响,研究其引起细胞凋亡的相关机制。方法采用不同浓度的TcdB处理SW480细胞,采用MTT法检测细胞增殖情况;用流式细胞术检测细胞的凋亡及线粒体膜电位变化情况。结果TcdB显著抑制了结肠癌SW480细胞的增殖,作用48 h后的抑制率为46.36%,呈一定的时间-浓度相关性;流式细胞仪检测结果表明,浓度为800 ng/ml的TcdB作用48 h,SW480细胞凋亡率为20.83%,呈一定的时间-浓度相关性。结论艰难梭菌毒素B能够抑制结肠癌SW480细胞增殖、诱导细胞凋亡,其机制可能与启动线粒体凋亡途径有关。 相似文献
66.
Matthew S. L. Lee Bharat Ramakrishna Alan C. Moss Howard S. Gold Westyn Branch‐Elliman 《Transplant infectious disease》2020,22(1)
We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high‐risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life‐saving cure. The patient had subsequent clinical improvement, however, developed multidrug‐resistant Pseudomonas aeruginosa bacteremia 2 days post‐procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk. 相似文献
67.
68.
69.
Epidemiology of Clostridium difficile Infection in a Large Population of Hospitalized US Military Veterans 总被引:2,自引:0,他引:2
The Patient Treatment File (PTF) of the Department of Veterans Affairs (VA) comprises the computerized records of all inpatients treated at all VA hospitals throughout the United States. The database was utilized to study the clinical epidemiology and impact of C. difficile colitis on health care among hospitalized US military veterans. The computerized medical records of 15,091 cases with C. difficile colitis and 61,931 controls without the diagnosis were extracted from the annual files between 1993 and 1998. Of all patients admitted to the hospital, 1% were diagnosed with C. difficile colitis, in 16% of whom it was listed as the primary discharge diagnosis. C. difficile colitis was more likely to occur in elderly white patients with multiple comorbid conditions. Compared with a control population of hospitalized patients without C. difficile colitis, the case population was subjected to more medical and surgical procedures and experienced longer hospital stays. The diagnosis of C. difficile colitis was associated with more frequent admissions to the intensive care unit and higher hospital-related and subsequent mortality. Eleven percent of the cases were admitted to hospital a second time after a mean of 202 days, 2.5% were readmitted a third time after an additional 182 days, and 0.8% were readmitted a fourth time after an additional 194 days. In conclusion, as old age, multiple comorbid conditions, a high number of medical and surgical intervention, and long hospitalization constitute the main risk factors for the development of C. difficile colitis, efforts at prevention should be directed primarily towards patients who present with these characteristics. 相似文献
70.