全文获取类型
收费全文 | 10321篇 |
免费 | 1662篇 |
国内免费 | 322篇 |
专业分类
耳鼻咽喉 | 50篇 |
儿科学 | 261篇 |
妇产科学 | 196篇 |
基础医学 | 3276篇 |
口腔科学 | 210篇 |
临床医学 | 1136篇 |
内科学 | 1531篇 |
皮肤病学 | 187篇 |
神经病学 | 554篇 |
特种医学 | 388篇 |
外国民族医学 | 2篇 |
外科学 | 482篇 |
综合类 | 957篇 |
现状与发展 | 2篇 |
预防医学 | 824篇 |
眼科学 | 189篇 |
药学 | 467篇 |
5篇 | |
中国医学 | 352篇 |
肿瘤学 | 1236篇 |
出版年
2024年 | 26篇 |
2023年 | 571篇 |
2022年 | 672篇 |
2021年 | 1152篇 |
2020年 | 1025篇 |
2019年 | 910篇 |
2018年 | 788篇 |
2017年 | 717篇 |
2016年 | 661篇 |
2015年 | 646篇 |
2014年 | 781篇 |
2013年 | 688篇 |
2012年 | 425篇 |
2011年 | 386篇 |
2010年 | 244篇 |
2009年 | 249篇 |
2008年 | 233篇 |
2007年 | 224篇 |
2006年 | 225篇 |
2005年 | 194篇 |
2004年 | 174篇 |
2003年 | 146篇 |
2002年 | 153篇 |
2001年 | 151篇 |
2000年 | 118篇 |
1999年 | 104篇 |
1998年 | 72篇 |
1997年 | 101篇 |
1996年 | 60篇 |
1995年 | 64篇 |
1994年 | 72篇 |
1993年 | 38篇 |
1992年 | 41篇 |
1991年 | 21篇 |
1990年 | 24篇 |
1989年 | 21篇 |
1988年 | 23篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 19篇 |
1984年 | 13篇 |
1983年 | 8篇 |
1982年 | 12篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 140 毫秒
71.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献72.
Massively parallel sequencing (MPS) applications in forensic science highlight the advantages of this technique compared to capillary electrophoresis (CE). The multiplexing of a wide range of genetic markers and access to the full amplicon sequence, allowing the detection of isoalleles, make it a very promising tool which could be applied to the most challenging casework DNA samples. However, the complexity of the manual library preparation protocol, potential DNA contamination and sample tracking issues are the main reasons why forensic scientists still hesitate to implement MPS analytical workflows in their laboratory. Here, we present the automation of all library preparation steps for up to 96 samples using the Verogen’s ForenSeq™ DNA Signature Preparation kit. This automated protocol, developed on a Hamilton ID STARlet robotic platform, is designed to allow the combined sequencing of rich and poor DNA samples thanks to a final step which adjusts normalized library pooling volume to guarantee a uniform depth of coverage across all samples. Our study includes tests of concordance, repeatability, reproducibility and sensitivity (1000 pg, 700 pg, 500 pg, 250 pg, 100 pg and 50 pg). Sequencing results obtained with the automated protocol were found to be concordant with previous validation studies using the manual protocol in terms of depth of coverage and allele coverage ratio. The results of this study will assist forensic laboratories seeking to acquire a plug and play solution to optimize the processing and analysis of casework samples with MPS. 相似文献
73.
The application of next‐generation sequencing (NGS) has enhanced our understanding of the genetic landscape in acquired aplastic anemia (AA). Parallel progress has been in addressing aspects underlying immune dysregulation in disease pathogenesis. Novel insights into the molecular and biologic mechanisms have led to a shift in the paradigm of AA, from a solely autoimmune pathogenic concept toward its recognition as a multifaceted pathophysiology characterized by cytogenetic abnormalities, recurrent somatic mutations, telomere attrition, and immune dysregulation. The detection of recurrent driver mutations disrupting myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)‐associated genes has suggested a pathophysiologic link between clonal hematopoiesis in AA and the later development of these clonal disorders. Further, certain AA‐related somatic genetic alterations may have clinical implications on treatment response, disease progression, and survival following immunosuppressive therapy. Going forward, wider validation of these genetic abnormalities will allow for their incorporation into a more informative risk stratification system that does not rely solely on clinical factors. 相似文献
74.
75.
《European journal of surgical oncology》2020,46(6):1080-1087
IntroductionRecent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis.Materials and methodsWe investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands.ResultsGEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11, FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1, SNAI2, and BIRC5, which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7.ConclusionWnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST. 相似文献
76.
77.
María C. Lanuza-López Sandra G. Martínez-Garza Jesús F. Solórzano-Vázquez Daniela Paz-Cervantes Claudia González-Ortega Israel Maldonado-Rosas 《Gynecological endocrinology》2020,36(9):829-834
AbstractOocyte maturation defect is a challenging situation in the management of infertility, the etiology may be related to endocrine causes, protocols used in ovarian stimulation, oocyte intrinsic defects or procedures in embryology laboratory. We report three Mexican females in treatment for primary infertility with non-mature oocytes after ovary stimulation and oocyte capture in whom a genetic diagnosis of TUBB8-oocyte maturation defect was revealed by exome sequencing. Two couples achieved pregnancies though oocyte donation after establishing the genetic etiology. Our results expand the role of TUBB8-disorders in patients of non-Asian ethnicity. Oocyte maturation defects of monogenic origin are a growing group of disorders that endocrinologists and reproductive medicine specialists should be aware in order to provide referral to genetics for establish a correct and opportune diagnosis. 相似文献
78.
79.
80.
目的探讨中医特色护理联合全程优质护理对心肌梗死后心律失常的应用效果。方法收集2017年1月-2018年12月收治的心肌梗死后心律失常患者88例,随机分为试验组和对照组,各44例。对照组患者予以全程优质护理。试验组患者予以全程优质护理联合中医特色护理。比较2组患者护理满意度及心理焦虑、抑郁评分。结果干预后2组心理焦虑、抑郁评分均降低(P<0.05);与对照组相比,试验组护理满意率较高,试验组心理焦虑、抑郁评分较低(P<0.05)。结论全程优质护理联合中医特色护理在心肌梗死后心律失常患者的护理中具有积极作用,能够改善心理健康状态。 相似文献