全文获取类型
收费全文 | 156篇 |
免费 | 47篇 |
专业分类
203篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 13篇 |
2014年 | 6篇 |
2013年 | 8篇 |
2012年 | 15篇 |
2011年 | 12篇 |
2010年 | 5篇 |
2009年 | 2篇 |
2008年 | 9篇 |
2007年 | 6篇 |
2006年 | 13篇 |
2005年 | 7篇 |
2004年 | 12篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 7篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1972年 | 1篇 |
1946年 | 1篇 |
排序方式: 共有203条查询结果,搜索用时 0 毫秒
71.
ABSTRACT: BACKGROUND: Malaria rapid diagnostic tests (RDTs) are protected from humidity-caused degradation by a desiccant added to the device packaging. The present study assessed malaria RDT products for the availability, type and design of desiccants and their information supplied in the instructions for use (IFU). METHODS: Criteria were based on recommendations of the World Health Organization (WHO), the European Community (CE) and own observations. Silica gel sachets were defined as selfindicating (all beads coated with a humidity indicator that changes colour upon saturation), partial-indicating (part of beads coated) and non-indicating (none of the beads coated). Indicating silica gel sachets were individually assessed for humidity saturation and (in case of partial-indicating silica gels) for the presence of indicating beads. RESULTS: Fifty malaria RDT products from 25 manufacturers were assessed, 14 (28%) products were listed by the "Global Fund Quality Assurance Policy" and 31 (62%) were CE-marked. All but one product contained a desiccant, mostly (47/50, 94%) silica gel. Twenty (40%) RDT products (one with no desiccant and 19 with non-indicating desiccant) did not meet the WHO guidelines recommending indicating desiccant. All RDT products with self- or partialindicating silica gel (n = 22 and 8 respectively) contained the toxic cobalt dichloride as humidity indicator. Colour change indicating humidity saturation was observed for 8/16 RDT products, at a median incidence of 0.8% (range 0.05%-4.6%) of sachets inspected. In all RDTs with partial-indicating silica gel, sachets with no colour indicating beads were found (median proportion 13.5% (0.6% - 17.8%) per product) and additional light was needed to assess the humidity colour. Less than half (14/30, 47%) IFUs of RDT products with indicating desiccants mentioned to check the humidity saturation before using the test. Information on properties, safety hazards and disposal of the desiccant was not included in any of the IFUs. There were no differences between Global Fund-listed and CE marked RDT products compared to those which were not. Similar findings were noted for a panel of 11 HIV RDTs that was assessed with the same checklist as the malaria RDTs. CONCLUSION: RDTs showed shortcomings in desiccant type and information supplied in the IFU. 相似文献
72.
Jeurissen A Billiau AD Moens L Shengqiao L Landuyt W Wuyts G Boon L Waer M Ceuppens JL Bossuyt X 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(1):529-536
Streptococcus pneumoniae causes serious infections in children, the elderly, and immunocompromised patients. Protection against infections with S. pneumoniae is mediated through Abs against the capsular polysaccharides (caps-PS). We previously showed that the murine Ab response to caps-PS is dependent on CD40-CD40L interaction. In the present paper, we addressed the question of whether the CD40-CD40L-mediated modulation of the anti-caps-PS immune reaction is the result of a direct interaction between B lymphocytes and T lymphocytes or of an indirect interaction. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice did not mount anti-caps-PS Abs. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice and CD4+ T lymphocytes from wild-type mice but not CD4+ T lymphocytes from CD40L knockout mice stimulated the anti-caps-PS Ab response. This indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in a CD40L-dependent manner. SCID/SCID mice reconstituted with B lymphocytes from CD40 knockout mice and CD4+ T lymphocytes from wild-type mice generated an anti-caps-PS Ab response that could be inhibited by MR1, a blocking anti-CD40L Ab. These data indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in an indirect way. Finally, lethally irradiated CD40 knockout mice reconstituted with bone marrow from wild-type mice mounted an anti-caps-PS Ab response that was comparable to the Ab response in wild-type mice, revealing that the required CD40 was on hemopoietic cells. In conclusion, we provide evidence that CD4+ T lymphocytes expressing CD40L stimulate the Ab response to soluble caps-PS by interacting with CD40-expressing non-B cells. 相似文献
73.
74.
The PAM-2000 portable chlorophyll fluorometer represents one of the first commercially available instruments utilizing the Pulse Amplitude Modulation (PAM) measurement principle, and has become a widely used platform for measuring chlorophyll fluorescence in a wide range of study systems. In this paper, we describe a new method for externally driving and gathering data from the PAM-2000, a method that allows the user to execute a pre-defined user run (or runs) and capture (1) rapid induction kinetics (at 2 ms frequency) during all saturating pulses, (2) measures of F, Fo, Fo′, Fm, and Fm′ associated with those same pulses, and (3) changes in fluorescence F at user-defined intervals between pulses, for the entire user run, with all data compressed into a single, manageable data logger file. Practically, the method makes possible, for example, a post-hoc evaluation of the appropriateness of saturation pulse lengths and intensities during a user run. More importantly it captures, during entire user runs, the varied information contained in slow changes in fluorescence between saturating pulses, as well as rapid induction kinetics, quenching coefficients and quantum yields all gathered simultaneously from all saturating flashes.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
75.
Anderson CA Pettersson FH Clarke GM Cardon LR Morris AP Zondervan KT 《Nature protocols》2010,5(9):1564-1573
This protocol details the steps for data quality assessment and control that are typically carried out during case-control association studies. The steps described involve the identification and removal of DNA samples and markers that introduce bias. These critical steps are paramount to the success of a case-control study and are necessary before statistically testing for association. We describe how to use PLINK, a tool for handling SNP data, to perform assessments of failure rate per individual and per SNP and to assess the degree of relatedness between individuals. We also detail other quality-control procedures, including the use of SMARTPCA software for the identification of ancestral outliers. These platforms were selected because they are user-friendly, widely used and computationally efficient. Steps needed to detect and establish a disease association using case-control data are not discussed here. Issues concerning study design and marker selection in case-control studies have been discussed in our earlier protocols. This protocol, which is routinely used in our labs, should take approximately 8 h to complete. 相似文献
76.
Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage. 总被引:9,自引:0,他引:9 下载免费PDF全文
K Chapman Z Mustafa C Irven A J Carr K Clipsham A Smith J Chitnavis J S Sinsheimer V A Bloomfield M McCartney O Cox L R Cardon B Sykes J Loughlin 《American journal of human genetics》1999,65(1):167-174
We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P=.05 were then taken through to the second stage, with an additional 184 families. This second stage confirmed evidence of linkage for markers on chromosome 11q. Additional markers from this region were then typed to create a denser map. We obtained a maximum single-point LOD score, at D11S901, of 2.40 (P=.0004) and a maximum multipoint-LOD score of 3.15, between markers D11S1358 and D11S35. A subset of 196 of the 481 families, comprising affected female sibling pairs, generated a corrected LOD score of 2.54 (P=.0003) for marker D11S901, with evidence for linkage extending 12 cM proximal to this marker. When we stratified for affected male sibling pairs there was no evidence of linkage to chromosome 11. Our data suggest that a female-specific susceptibility gene for idiopathic osteoarthritis is located on chromosome 11q. 相似文献
77.
Extent and distribution of linkage disequilibrium in three genomic regions 总被引:36,自引:0,他引:36 下载免费PDF全文
Abecasis GR Noguchi E Heinzmann A Traherne JA Bhattacharyya S Leaves NI Anderson GG Zhang Y Lench NJ Carey A Cardon LR Moffatt MF Cookson WO 《American journal of human genetics》2001,68(1):191-197
The positional cloning of genes underlying common complex diseases relies on the identification of linkage disequilibrium (LD) between genetic markers and disease. We have examined 127 polymorphisms in three genomic regions in a sample of 575 chromosomes from unrelated individuals of British ancestry. To establish phase, 800 individuals were genotyped in 160 families. The fine structure of LD was found to be highly irregular. Forty-five percent of the variation in disequilibrium measures could be explained by physical distance. Additional factors, such as allele frequency, type of polymorphism, and genomic location, explained <5% of the variation. Nevertheless, disequilibrium was occasionally detectable at 500 kb and was present for over one-half of marker pairs separated by <50 kb. Although these findings are encouraging for the prospects of a genomewide LD map, they suggest caution in interpreting localization due to allelic association. 相似文献
78.
Hanne Hoskens Dongjing Liu Sahin Naqvi Myoung Keun Lee Ryan J. Eller Karlijne Indencleef Julie D. White Jiarui Li Maarten H. D. Larmuseau Greet Hens Joanna Wysocka Susan Walsh Stephen Richmond Mark D. Shriver John R. Shaffer Hilde Peeters Seth M. Weinberg Peter Claes 《PLoS genetics》2021,17(5)
The analysis of contemporary genomic data typically operates on one-dimensional phenotypic measurements (e.g. standing height). Here we report on a data-driven, family-informed strategy to facial phenotyping that searches for biologically relevant traits and reduces multivariate 3D facial shape variability into amendable univariate measurements, while preserving its structurally complex nature. We performed a biometric identification of siblings in a sample of 424 children, defining 1,048 sib-shared facial traits. Subsequent quantification and analyses in an independent European cohort (n = 8,246) demonstrated significant heritability for a subset of traits (0.17–0.53) and highlighted 218 genome-wide significant loci (38 also study-wide) associated with facial variation shared by siblings. These loci showed preferential enrichment for active chromatin marks in cranial neural crest cells and embryonic craniofacial tissues and several regions harbor putative craniofacial genes, thereby enhancing our knowledge on the genetic architecture of normal-range facial variation. 相似文献
79.
80.
Upon cell entry, the genomes of herpes simplex virus type 1 (HSV-1) and adenovirus (Ad) associate with distinct nuclear structures termed ND10 or promyelocytic leukemia (PML) nuclear bodies (NBs). PML NB morphology is altered or disrupted by specific viral proteins as replication proceeds. We examined whether adeno-associated virus (AAV) replication compartments also associate with PML NBs, and whether modification or disruption of these by HSV-1 or Ad, both of which are helper viruses for AAV, is necessary at all. Furthermore, to add a fourth dimension to our present view of AAV replication, we established an assay that allows visualization of AAV replication in live cells. A recombinant AAV containing 40 lac repressor binding sites between the AAV inverted terminal repeats was constructed. AAV Rep protein and helper virus-mediated replication of this recombinant AAV genome was visualized by binding of enhanced yellow fluorescent protein-lac repressor fusion protein to double-stranded AAV replication intermediates. We demonstrate in live cells that AAV DNA replication occurs in compartments which colocalize with AAV Rep. Early after infection, the replication compartments were small and varied in numbers from 2 to more than 40 per cell nucleus. Within 4 to 8 h, individual small replication compartments expanded and fused to larger structures which filled out much of the cell nucleus. We also show that AAV replication compartments can associate with modified PML NBs in Ad-infected cells. In wild-type HSV-1-infected cells, AAV replication compartments and PML NBs did not coexist, presumably because PML was completely disrupted by the HSV-1 ICP0 protein. However, alteration or disruption of PML appears not to be a prerequisite for AAV replication, as the formation of replication compartments was normal when the ICP0 mutants HSV-1 dl1403 and HSV-1 FXE, which do not affect PML NBs, were used as the helper viruses; under these conditions, AAV replication compartments did not associate with PML NBs. 相似文献