全文获取类型
收费全文 | 939篇 |
免费 | 76篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 20篇 |
妇产科学 | 21篇 |
基础医学 | 126篇 |
口腔科学 | 99篇 |
临床医学 | 81篇 |
内科学 | 217篇 |
皮肤病学 | 11篇 |
神经病学 | 130篇 |
特种医学 | 24篇 |
外科学 | 72篇 |
综合类 | 7篇 |
一般理论 | 1篇 |
预防医学 | 67篇 |
眼科学 | 26篇 |
药学 | 68篇 |
中国医学 | 1篇 |
肿瘤学 | 45篇 |
出版年
2024年 | 1篇 |
2023年 | 9篇 |
2022年 | 25篇 |
2021年 | 39篇 |
2020年 | 34篇 |
2019年 | 41篇 |
2018年 | 45篇 |
2017年 | 23篇 |
2016年 | 43篇 |
2015年 | 29篇 |
2014年 | 50篇 |
2013年 | 46篇 |
2012年 | 87篇 |
2011年 | 75篇 |
2010年 | 38篇 |
2009年 | 43篇 |
2008年 | 68篇 |
2007年 | 62篇 |
2006年 | 54篇 |
2005年 | 44篇 |
2004年 | 43篇 |
2003年 | 49篇 |
2002年 | 33篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有1018条查询结果,搜索用时 0 毫秒
1.
2.
Mariela Dutra Gontijo Moura Soraya de Mattos Camargo Grossmann Linaena Méricy da Silva Fonseca Maria Inês Barreiros Senna Ricardo Alves Mesquita 《Journal of oral pathology & medicine》2006,35(6):321-326
BACKGROUND: Oral hairy leukoplakia (OHL) may be an indicator of the progression of Human Immunodeficiency Virus (HIV)-induced immuno-depression, and the evaluation of risk factors leading to OHL is important in the management of these HIV-infected patients. However, there are few studies that analyze risk factors leading to OHL in the Brazilian population. The aim of this case-control study is to present data about prevalence rates and risk factors leading to OHL in a sample of HIV-infected adults in Brazil. METHODS: This case-control study included 111 HIV-infected patients treated at a clinic for sexually transmitted diseases and HIV. In the initial examinations with dentists, variables were collected from all patients. Diagnosis of OHL was performed in accordance with the International Classification System and cytological features. The Fisher and the chi-squared tests were used for statistical analysis. The proportional prevalence and odds ratio were estimated. RESULTS: Outcome presented a positive, statistically significant association among the presence of OHL and viral load of 3000 copies/mul or greater (P = 0.0001; odds ratio (OR) = 5.8), presence of oral candidiasis (P = 0.0000; OR = 11.1), previous use of fluconazole (P = 0.0000; OR = 24.6), and use of systemic acyclovir (P = 0.032; OR = 4.3). Antiretroviral medication presented a negative, statistically significant association with the presence of OHL (P = 0.002; OR = 8.4). CONCLUSIONS: Prevalence of OHL was 28.8%. Viral load, oral candidiasis, previous use of fluconazole, and systemic acyclovir were determined to be risk factors for OHL. Antiretroviral medication proved to be protective against the development of OHL. 相似文献
3.
4.
Rectal diazepam in the treatment of absence status: a pharmacodynamic study 总被引:7,自引:1,他引:6
下载免费PDF全文
![点击此处可从《Journal of neurology, neurosurgery, and psychiatry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Norman Milligan Soraya Dhillon Alan Richens Jolyon Oxley 《Journal of neurology, neurosurgery, and psychiatry》1981,44(10):914-917
Rectal administration of diazepam is highly effective in terminating absence status as judged by reduction of spike-wave activity in the EEG. Pharmacokinetic studies indicate that diazepam can have antiepileptic properties at serum levels well below those previously reported as being necessary to achieve a therapeutic effect. 相似文献
5.
An eighth locus for autosomal dominant retinitis pigmentosa is linked to chromosome 17q 总被引:5,自引:2,他引:5
Bardienb Soraya; Ebenezer Neil; Greenberg Jacquie; Inglehearn Chris F.; Bartmann Lecia; Goliath Rene; Beighton Peter; Ramesar Rajkumar; Bhattacharya Shomi S. 《Human molecular genetics》1995,4(8):1459-1462
Retinitis pigmentosa is one of the most common causes of severevisual handicap in middle to late life. Prior to this report,seven loci had previously been mapped for the autosomal dominantform of this disorder (adRP). We now report the identificationof a novel adRP locus on chromosome 17q. To map the new locus,we performed linkage analysis with microsatellite markers ina large South African kindred. After exclusion of 13 RP candidategene loci (including rhodopsin and peripherin-RDS), we obtainedsignificant positive lod scores at zero recombination fraction( 相似文献
6.
Shobana Sekar Livia Tomasini Christos Proukakis Taejeong Bae Logan Manlove Yeongjun Jang Soraya Scuderi Bo Zhou Maria Kalyva Anahita Amiri Jessica Mariani Fritz J. Sedlazeck Alexander E. Urban Flora M. Vaccarino Alexej Abyzov 《Genome research》2020,30(12):1695
Somatic mosaicism, manifesting as single nucleotide variants (SNVs), mobile element insertions, and structural changes in the DNA, is a common phenomenon in human brain cells, with potential functional consequences. Using a clonal approach, we previously detected 200–400 mosaic SNVs per cell in three human fetal brains (15–21 wk postconception). However, structural variation in the human fetal brain has not yet been investigated. Here, we discover and validate four mosaic structural variants (SVs) in the same brains and resolve their precise breakpoints. The SVs were of kilobase scale and complex, consisting of deletion(s) and rearranged genomic fragments, which sometimes originated from different chromosomes. Sequences at the breakpoints of these rearrangements had microhomologies, suggesting their origin from replication errors. One SV was found in two clones, and we timed its origin to ∼14 wk postconception. No large scale mosaic copy number variants (CNVs) were detectable in normal fetal human brains, suggesting that previously reported megabase-scale CNVs in neurons arise at later stages of development. By reanalysis of public single nuclei data from adult brain neurons, we detected an extrachromosomal circular DNA event. Our study reveals the existence of mosaic SVs in the developing human brain, likely arising from cell proliferation during mid-neurogenesis. Although relatively rare compared to SNVs and present in ∼10% of neurons, SVs in developing human brain affect a comparable number of bases in the genome (∼6200 vs. ∼4000 bp), implying that they may have similar functional consequences.Somatic mosaicism, the presence of more than one genotype in the somatic cells of an individual, is a prominent phenomenon in the human central nervous system. Forms of mosaicism include aneuploidies and smaller copy number variants (CNVs), structural variants (SVs), mobile element insertions, indels, and single nucleotide variants (SNVs). The developing human brain exhibits high levels of aneuploidy compared to other tissues, generating genetic diversity in neurons (Pack et al. 2005; Yurov et al. 2007; Bushman and Chun 2013). Such aneuploidy was suggested to be a natural feature of neurons, rather than a distinctive feature of neurodegeneration. However, the frequency of aneuploidy in neurons has been debated, with a separate study suggesting that aneuploidies occur in only about 2.2% of mature adult neurons (Knouse et al. 2014). They hence infer that such aneuploidy could have adverse effects at the cellular and organismal levels. Additionally, analysis of single cells from normal and pathological human brains identified large, private, and likely clonal somatic CNVs in both normal and diseased brains (Gole et al. 2013; McConnell et al. 2013; Cai et al. 2014; Knouse et al. 2016; Chronister et al. 2019; Perez-Rodriguez et al. 2019), with 3%–25% of human cerebral cortical nuclei carrying megabase-scale CNVs (Chronister et al. 2019) and deletions being twice as common as duplications (McConnell et al. 2013). Given that CNVs often arise from nonhomologous recombination and replication errors, their likely time of origin is during brain development. However, when CNVs first arise in human brain development has not yet been investigated. The present work is the first to examine this question using clonal populations of neuronal progenitor cells (NPCs) obtained from fetal human brains.Detection of CNVs in single neurons is challenging, given the need to amplify DNA. Such amplification may introduce artifacts that could, in turn, be misinterpreted as CNVs. In order to address this technical limitation, Hazen et al. reprogrammed adult postmitotic neurons using somatic cell nuclear transfer (SCNT) of neuronal nuclei into enucleated oocytes (Hazen et al. 2016). These oocytes then made sufficient copies of the neuronal genome allowing for whole-genome sequencing (WGS), thus eliminating the need for amplification in vitro. Using this method, they identified a total of nine structural variants in six neurons from mice, three of which were complex rearrangements. However, it is not possible to extend such studies to humans, given the ethical issues involved, besides the technical challenges in obtaining and cloning adult neurons. To circumvent the need of single-cell DNA amplification or nuclear cloning, we examined clonal cell populations obtained from neural progenitor cells from the frontal region of the cerebral cortex (FR), parietal cortex (PA) and basal ganglia (BG) and describe here the discovery and analysis of mosaic SVs in these NPCs (Bae et al. 2018). These clones were sequenced at 30× coverage (much higher than most previous single-cell studies), allowing identification of SVs other than large deletions and duplications as well as precise breakpoint resolution. 相似文献
7.
Valles S Caunt CJ Walker MH Qwarnstrom EE 《Laboratory investigation; a journal of technical methods and pathology》2002,82(7):855-862
This study shows that increase in IL-1 receptor levels by platelet derived growth factor (PDGF) involves an enhancement of a matrix-dependent, low-affinity receptor that constitutes a heparan sulfate. Fibronectin attachment caused pronounced alterations in IL-1 receptor function in smooth muscle cells, involving a pronounced increase in cell surface binding from an average of 2,000 up to approximately 8,000 receptors/cell and an increase in affinity (K(a)) of the type I receptor from 1.8 +/- 0.9 x 10(9) to 3.7 +/- 0.5 x 10(9) M(-1). PDGF stimulation similarly enhanced the level of cell surface binding by between 30% and 100%, with, in general, less effect on cells plated on fibronectin. Further, PDGF had a pronounced effect on the type I receptor affinity in the absence of matrix attachment, increasing the K(a) from 1.77 +/- 0.93 x 10(9) to 5.1 +/- 2.1 x 10(9) M(-1). Scatchard analyses revealed that PDGF, similarly to fibronectin attachment, caused enhancement of a second low-affinity binding site. Antibody blocking showed that approximately 50% of the attachment-induced increase was independent of type I receptor binding. Further, a similar fraction of the cell surface interaction was blocked by soluble heparan sulfate and dependent on cell binding to the heparan binding site. Cross-linking demonstrated that, in addition to the type I receptor, IL-1 bound to a second high molecular weight complex of 300 kd, induced by fibronectin attachment as well as by PDGF in the absence of matrix. Biochemical analyses demonstrated that this second site constitutes a heparan sulfate, which directly interacted with the type I receptor after recruitment to the complex, and which bound up to 50% and 25% of the ligand after fibronectin attachment and PDGF stimulation, respectively. The data show that PDGF induces an attachment-regulated low-affinity IL-1 binding site in smooth muscle cells, constituting a heparan sulfate. Correlation of the recruitment of this component to the IL-1 receptor complex with structural regulation of receptor function and enhancement of IL-1-mediated responses suggests that this is a significant mechanism in PDGF augmentation of local inflammatory responses during vessel wall pathogenesis. 相似文献
8.
9.
Purification and partial characterization of a Paracoccidioides brasiliensis protein with capacity to bind to extracellular matrix proteins
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
González A Gómez BL Diez S Hernández O Restrepo A Hamilton AJ Cano LE 《Infection and immunity》2005,73(4):2486-2495
Microorganisms adhere to extracellular matrix proteins by means of their own surface molecules. Paracoccidioides brasiliensis conidia have been shown to be capable of interacting with extracellular matrix proteins. We aimed at determining the presence of fungal proteins that could interact with extracellular matrix protein and, if found, attempt their purification and characterization. Various extracts were prepared from P. brasiliensis mycelial and yeast cultures (total homogenates, beta-mercaptoethanol, and sodium dodecyl sulfate [SDS] extracts) and analyzed by ligand affinity assays with fibronectin, fibrinogen and laminin. Two polypeptides were detected in both fungal forms. SDS extracts that interacted with all the extracellular matrix protein were tested; their molecular masses were 19 and 32 kDa. Analysis of the N-terminal amino acid sequence of the purified 32-kDa mycelial protein showed substantial homology with P. brasiliensis, Histoplasma capsulatum, and Neurospora crassa hypothetical proteins. Additionally, a monoclonal antibody (MAb) produced against this protein recognized the 32-kDa protein in the SDS extracts of both fungal forms for immunoblot. Immunofluorescence analysis revealed that this MAb reacted not only with mycelia and yeast cells, but also with conidia, indicating that this protein was shared by the three fungal propagules. By immunoelectron microscopy, this protein was detected in the cell walls and in the cytoplasm. Both the 32-kDa purified protein and MAb inhibited the adherence of conidia to the three extracellular matrix proteins in a dose-dependent manner. These findings demonstrate the presence of two polypeptides capable of interacting with extracellular matrix proteins on the surface of P. brasiliensis propagules, indicating that there may be common receptors for laminin, fibronectin, and fibrinogen. These proteins would be crucial for initial conidial adherence and perhaps also in dissemination of paracoccidioidomycosis. 相似文献
10.
Soraya D. Varella Gilberto L. Pozetti Wagner Vilegas Eliana Ap. Varanda 《Toxicology in vitro》2004,18(6):895-900
The mutagenic activity of waste material originating from an aluminum products factory was determined by the Salmonella/microsome assay, using the bacterial strains TA100, TA98 and YG1024. The material was obtained by sweeping the factory floor at the end of the work shift. Organic compounds were extracted by ultrasound for 30 min in dichloromethane or 70% ethanol. After evaporation of solvent, these extracts were dissolved in dimethylsulfoxide, and tested for the mutagenic activity at varying concentrations. All the extracts from the factory had mutagenic activity, especially in the YG1024 strain, suggesting the presence of aromatic amines, later confirmed by chemical analysis. The TA98 strain also showed mutagenic activity, though it did not exhibit the highest mutagenicity index observed with the YG1024 strain. In TA100, mutagenic activity was not observed. This study should serve as an alert to management and those who are occupationally exposed, and as a warning that this type of waste should not be discarded in the environment without any control. 相似文献