首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   734篇
  免费   22篇
  国内免费   10篇
耳鼻咽喉   1篇
儿科学   13篇
妇产科学   3篇
基础医学   261篇
口腔科学   8篇
临床医学   79篇
内科学   121篇
皮肤病学   18篇
神经病学   31篇
特种医学   16篇
外科学   18篇
综合类   76篇
预防医学   55篇
眼科学   3篇
药学   18篇
中国医学   6篇
肿瘤学   39篇
  2022年   3篇
  2021年   2篇
  2020年   5篇
  2019年   4篇
  2018年   7篇
  2017年   13篇
  2016年   12篇
  2015年   7篇
  2014年   15篇
  2013年   28篇
  2012年   15篇
  2011年   27篇
  2010年   22篇
  2009年   21篇
  2008年   33篇
  2007年   34篇
  2006年   39篇
  2005年   36篇
  2004年   22篇
  2003年   30篇
  2002年   43篇
  2001年   26篇
  2000年   41篇
  1999年   26篇
  1998年   17篇
  1997年   17篇
  1996年   19篇
  1995年   28篇
  1994年   40篇
  1993年   18篇
  1992年   28篇
  1991年   26篇
  1990年   12篇
  1989年   15篇
  1988年   16篇
  1987年   9篇
  1986年   5篇
  1985年   4篇
  1984年   1篇
排序方式: 共有766条查询结果,搜索用时 15 毫秒
1.
Objective: Genome-wide association studies (GWAS) have identified a number of genetic variants associated with the susceptibility of bladder cancer (BC) in European and Chinese populations. Here, we assessed the association of two of these variants, rs9642880 and rs710521 in an Egyptian patients and also examined the expression of c-Myc.The basis was due to the absence of studies on Egyptian patients to determine the association between rs9642880& rs710521 and bladder cancer risk, particularly due to the known role of the variant (rs9642880) in the Progression and development of bladder cancer. Methods: Urine samples were collected from onehundred and fiftybladder cancer patients under particular standards and fifty healthy controls. Genomic DNA was extracted,  rs9642880 G>T and rs710521 A>G polymorphisms were amplified, assessed via restriction fragment length polymorphism(RFLP) and sequenced. Urine retrieved results were compared to the histopathological diagnosis of tissue biopsies and to the results of C-Myc immunohistochemistry. Data were statistically analyzed using Microsoft Excel 2016, association between significant genotypes of the two studied variables and bladder cancer risk was performed. Results: We found that the TT genotype of rs9642880 G>T was strongly associated with the risk of bladder cancer, andfor rs710521 A>G, AG genotype was also identified to has an association with bladder cancer risk.All 150 tumor sections showed positive immunoreactivity for c-Myc in the nucleus and the cytoplasm. Conclusion: Identifying the association to risk of bladder cancer using genetic analysis will help in the early detection of the disease.  相似文献   
2.
BackgoundConventional diagnosis of invasive fungal disease from blood cultures is often notoriously delayed and inadequately sensitive. We aimed to develop a universal primers-based polymerase chain reaction (PCR) assay and restriction fragment length polymorphisms (RFLP) for rapid identification of invasive fungal disease (IFD).MethodsWe evaluated 16 clinical fungal species using a combination of PCR assays with 3 different restriction endonucleases targeting various internal transcribed spacer (ITS) regions and high resolution melting analysis (HRMA). Serial samples from 75 patients suspected to have IFD were analyzed for clinical verification.ResultsWe have designed a universal PCR capable of amplifying a portion of the 18S rRNA gene of 16 clinically important fungal species. The restriction patterns of most PCR products generated by EcoRI or double digested by ClaI and AvaI were different, except Aspergillus niger and Aspergillus flavus had a similar pattern, and Aspergillus fumigatus and Aspergillus terreus had a similar pattern. All these species had a unique melting curve shape using the HRMA. Both HRMA and universal PCR had adequate sensitivity, and all sixteen reference fungal species can be clearly distinguished by the universal PCR-RFLP-HRMA assay. With a reference library of 176 clinically relevant fungal strains, and 75 clinical samples from patients with suspicious IFD were tested, our assay identified 100% and 61.1% of isolates from the reference library and clinical samples, respectively.ConclusionsUniversal PCR and RFLP coupled with HRMA could be a highly discriminative and useful molecular diagnostic that could enhance the current diagnostic, treatment, and surveillance methods of invasive fungal disease.  相似文献   
3.
Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that causes reproductive failure in sows and respiratory problems in piglets. PRRSV infection leads to substantial pig mortality and causing huge economic losses so that disease outbreaks caused by the new PRRSV strain from other regions have caused great concern in China. In this study, we analysed the pathogenicity of the novel ORF5 RFLP 1‐7‐4‐like PRRSV strain, named PRRSV‐ZDXYL‐China‐2018‐1 in pigs. The viral challenge test showed that PRRSV‐ZDXYL‐China‐2018‐1 infection can cause persistent fever, moderate dyspnoea, serum viraemia and interstitial pneumonia in piglets. The levels of viral loads in serum and PRRSV‐specific antigen were also detected in lung tissues were used one‐step Taq‐Man RT‐qPCR and Immunohistochemistry, respectively. At 28dpi, the level of specific antibodies was increased among infected piglets. Importantly, the new virus appeared be a moderately virulent isolate with pathogenicity compared to HP‐PRRSV strain LQ (JXA1‐like strain). Histological examination revealed severe monocyte haemorrhage and interstitial pneumonia associated with monocyte infiltration in the lung tissue of pigs infected with PRRSV‐ZDXYL‐China‐2018‐1 and LQ‐JXA1 strains. Immunohistochemistry (IHC) results showed positive brown‐red epithelial cells and macrophages in pig lungs. Therefore, it is critical to establish an effective strategy to control the spread of PRRSV in China.  相似文献   
4.
目的:调查云南省大叶千斤拔(Flemingia macrophylla)与细叶千斤拔(Flemingia lineata)根内丛枝菌根真菌(Arbuscular Mycorrhizal Fungi,AMF)群落结构多样性。方法:使用巢式-PCR、克隆、限制性片段长度多态性(Restriction Fragment Length Polymorphism,RFLP)分析及测序技术。结果:共获得558个含有丛枝菌根真菌18S rRNA片段的克隆子,经RFLP分析后得到83个RFLP类型,DNA序列分析可将其划分为23个可操作分类单元(Operational Taxonomic Units,OTUs),分属于5个科,Glomeraceae为优势类群。在MaarjAM数据库中进行比对后,23个OTUs可鉴定为18个虚拟分类分子种,分布于13种不同的生境。经统计分析大叶千斤拔与细叶千斤拔根内丛枝菌根真菌群落组成比较,差异有统计学意义(P<0.001)。结论:比较大叶千斤拔与细叶千斤拔根内丛枝菌根真菌群落差异,结合丛枝菌根真菌在生态系统中的分布特点,为种植千斤拔属植物的选址提供有力地环境指标数据,并为筛选促生菌株提供依据。  相似文献   
5.
Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin’s lymphoma (NHL), this pilot study was designed to investigate the impact of CD38 (184C/G; rs6449182) and IL-6 (?174 G/C; rs1800795) gene polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma (DLBCL); major types of NHL. To the best of our knowledge, this study is the first one that examines CD38 polymorphism in the NHL. Genotyping polymorphism is performed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for CD38 and Mutagenically separated PCR (MS-PCR) for IL-6 in 100 Egyptian NHL patients with DLBCL subtype and 119 normal controls. The serum level of IL-6 was measured using Enzyme-linked immunosorbent assay (ELISA). CD38 (184C/G) genotype is significantly increased in NHL patients (p?<?0.01), while the GG genotype is significantly increased in controls (p?<?0.05). Only two genotypes were found (GG and GC) in IL-6 (?174), no CC in our NHL patients and only one case in the controls. Insignificant change in IL-6 (?174 G/C) genotypes was recorded. Significantly increased serum IL-6 (p?<?0.05) was positively correlated (r?=?0.17; p?<?0.05) with the disease. Taken together, our data stressed the importance of CD38 gene polymorphism in developing DLBCL. Our pilot study indicates that CD38 (184) CG genotype might play a role in DLBCL susceptibility in Egyptians. Additional prospective studies on larger population are needed to confirm our findings.  相似文献   
6.
Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked Immunosorbent Assay [ELISA], VDR (FokI, BsmI) gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR–RFLP].Serum levels of calcium, phosphorus, alkaline phosphatase and ferritin were determined in 50 Pediatrics beta thalassemia major patients and 60 controls. Patients had significantly lower serum calcium (p < 0.001) lower serum vitamin D3 (p < 0.001) with elevated levels of phosphorus (p < 0.001) and alkaline phosphatase than controls (p = 0.04). Of the patients studied, 60 % had vitamin D deficiency (<20 ng/ml), 20 % had vitamin D insufficiency (21–30 ng/ml) and 20 % had sufficient vitamin D status (>30 ng/ml). Patients harboring mutant (Ff,ff) and wild (BB) genotypes were associated with lower serum calcium (p = 0.08, 0.02) respectively, lower vitamin D3 levels (p < 0.001, 0.01) respectively. They were also suffering from more bony complications although the difference was not statistically significant (p > 0.05). In conclusion, these results suggest that the VDR (FokI, BsmI) gene polymorphisms influence vitamin D status, (Ff,ff), BB genotypes had lower vitamin D levels, so they might influence risk of development of bone diseases in beta thalassemia major.  相似文献   
7.

Background:

The trematodes of the genus Fasciola (the liver flukes) are among the well-known instances of food-borne parasites worldwide. Differentiation of Fasciola species is important because of their different transmission and epidemiological characteristics. The current study was undertaken to discriminate Fasciola species in the domestic ruminants of Urmia city, Iran.

Methods:

Adult flukes were isolated from the naturally infected livers of the slaughtered water buffaloes and sheep. The flukes were initially identified based on morphological and morphometric parameters. A 618-bp-long fragment of the 28SrRNA gene of Fasciola was amplified by polymerase chain reaction (PCR). The amplified fragment was digested by DraII or AvaII enzymes for a restriction fragment length polymorphism (RFLP) analysis and sequenced for the phylogenetic tree construction.

Results:

Based on the morphometric examination, the flukes belonged to F. hepatica, F. gigantica and an intermediate Fasciola form. The PCR-RFLP analysis was able to differentiate F. hepatica from F. gigantica. While the phylogenetic reconstruction justified, to some extent, the morphological diagnosis, it failed to segregate F. hepatica from F. gigantica identified in this and the previous studies.

Conclusion:

To resolve fully the problem of taxonomy and evolution in Fasciola species, employing a broad range of molecular and morphological approaches is necessary. This is crucial for epidemiological surveys and successful clinical management of their infection.  相似文献   
8.

Background

Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.

Methods

A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR–RFLP and real-time PCR.

Results

Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 −260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20–10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41–0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).

Conclusions

Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.  相似文献   
9.
Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.  相似文献   

10.
Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR–RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号