全文获取类型
收费全文 | 126篇 |
免费 | 5篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 9篇 |
2012年 | 6篇 |
2011年 | 10篇 |
2010年 | 12篇 |
2009年 | 9篇 |
2008年 | 8篇 |
2007年 | 8篇 |
2006年 | 4篇 |
2005年 | 3篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
排序方式: 共有131条查询结果,搜索用时 31 毫秒
101.
Robert S. Jansen Hilde Rosing Wiete Kromdijk Rob ter Heine Jan HM Schellens Jos H. Beijnen 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(7-8):621-627
Emtricitabine (FTC) and tenofovir (TFV) are widely used antiviral agents that require intracellular phosphorylation to become active. This article describes the development and validation of an assay for the simultaneous quantification of FTC mono-, di- and triphosphate (FTC-MP, -DP and -TP), TFV and TFV mono- and diphosphate (TFV-MP and -DP) in peripheral blood mononuclear cells. Reference compounds and internal standards were obtained by thermal degradation of FTC-TP, TFV-DP, stable isotope-labeled TFV-DP and stable isotope-labeled cytosine triphosphate. Cells were lysed in methanol:water (70:30, v/v) and the extracted nucleotides were analyzed using weak anion-exchange chromatography coupled with tandem mass spectrometry. Calibration ranges in PBMC lysate from 0.727 to 36.4, 1.33 to 66.4 and 1.29 to 64.6 nM for FTC-MP, FTC-DP and FTC-TP and from 1.51 to 75.6, 1.54 to 77.2 and 2.54 to 127 nM for TFV, TFV-MP and TFV-DP, respectively, were validated. Accuracies were within ?10.3 and 16.7% deviation at the lower limit of quantification at which the coefficients of variation were less than 18.2%. At the other tested levels accuracies were within ?14.3 and 9.81% deviation and the coefficients of variation lower than 14.7%. The stability of the compounds was assessed under various analytically relevant conditions. The method was successfully applied to clinical samples. 相似文献
102.
Screening of Probiotic Activities of Forty-Seven Strains of Lactobacillus spp. by In Vitro Techniques and Evaluation of the Colonization Ability of Five Selected Strains in Humans 总被引:4,自引:0,他引:4 下载免费PDF全文
C. N. Jacobsen V. Rosenfeldt Nielsen A. E. Hayford P. L. Mller K. F. Michaelsen A. Prregaard B. Sandstrm M. Tvede M. Jakobsen 《Applied microbiology》1999,65(11):4949-4956
The probiotic potential of 47 selected strains of Lactobacillus spp. was investigated. The strains were examined for resistance to pH 2.5 and 0.3% oxgall, adhesion to Caco-2 cells, and antimicrobial activities against enteric pathogenic bacteria in model systems. From the results obtained in vitro, five strains, Lactobacillus rhamnosus 19070-2, L. reuteri DSM 12246, L. rhamnosus LGG, L. delbrueckii subsp. lactis CHCC 2329, and L. casei subsp. alactus CHCC 3137, were selected for in vivo studies. The daily consumption by 12 healthy volunteers of two doses of 1010 freeze-dried bacteria of the selected strains for 18 days was followed by a washout period of 17 days. Fecal samples were taken at days 0 and 18 and during the washout period at days 5 and 11. Lactobacillus isolates were initially identified by API 50CHL and internal transcribed spacer PCR, and their identities were confirmed by restriction enzyme analysis in combination with pulsed-field gel electrophoresis. Among the tested strains, L. rhamnosus 19070-2, L. reuteri DSM 12246, and L. rhamnosus LGG were identified most frequently in fecal samples; they were found in 10, 8, and 7 of the 12 samples tested during the intervention period, respectively, whereas reisolations were less frequent in the washout period. The bacteria were reisolated in concentrations from 105 to 108 cells/g of feces. Survival and reisolation of the bacteria in vivo appeared to be linked to pH tolerance, adhesion, and antimicrobial properties in vitro. 相似文献
103.
Jessica AB van Nies Celina Alves Audrey LS Radix-Bloemen Cécile Gaujoux-Viala Tom WJ Huizinga Johanna MW Hazes Elisabeth Brouwer Bruno Fautrel Annette HM van der Helm-van Mil 《Arthritis research & therapy》2015,17(1)
IntroductionMorning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA).MethodsIn arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions.ResultsIn arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver operating characteristic curve (AUCs) were low (0.52, 0.57, 0.54). In early arthritis, morning stiffness was associated with 2010-RA independent of other predictors (Leiden EAC OR 1.72 (95% CI 1.31 to 2.25, AUC 0.68), ESPOIR OR 1.68 (1.03 to 2.74, AUC 0.64)). Duration of ≥30 minutes provided optimal discrimination for RA in early arthritis. Morning stiffness was not associated with radiological progression or DMARD-free sustained remission.ConclusionsMorning stiffness in arthralgia and early arthritis is associated with arthritis and RA respectively. This supports the incorporation of morning stiffness in the diagnostic process.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0616-3) contains supplementary material, which is available to authorized users. 相似文献104.
Azza M. Elamir Olfat G. Shaker Mohamed HM. El-Komy Mai Mahmoud sharabi Nesreen M. Aboraia 《Biochemistry and Biophysics Reports》2021
BackgroundPsoriasis is a chronic skin disorder manifested by recurrent episodes of scaly, red, itchy skin patches that occur within apparently normal skin.ObjectivesThis study was performed to detect the expression of serum and tissue (lesion and non-lesion) LncRNA MALAT-1 and MiRNA-9 that might be used as biomarkers for psoriasis.MethodsBlood samples were obtained from 60 psoriasis patients and 40 controls, as well as 4 mm punch biopsy from lesional and non lesional skin of psoriatic patient and normal skin of healthy controls. Expression of LncRNA MALAT-1 and miRNNA-9 in serum and tissues was detected by real time qRT-PCR.Resultsa statistically significant increase in the expression of MALAT-1 in lesional and non-lesional skin and serum of psoriatic patients in comparison to controls were detected. Moreover, there was statistically significant increase in serum MiRNA-9 in patients in comparison to controls, while its tissue level was significantly lower in patients.ConclusionThis study highlights the dysregulation of LncRNA MALAT-1 and miRNA-9 in psoriasis. Elevated expression of MALAT-1 in lesional skin of psoriatic patients compared to non-lesional skin may possibly contribute to the development of psoriatic plaques. 相似文献
105.
Shuying Sun Zhengyi Chen Pearlly S Yan Yi-Wen Huang Tim HM Huang Shili Lin 《BMC bioinformatics》2011,12(1):54
Background
DNA methylation has been shown to play an important role in the silencing of tumor suppressor genes in various tumor types. In order to have a system-wide understanding of the methylation changes that occur in tumors, we have developed a differential methylation hybridization (DMH) protocol that can simultaneously assay the methylation status of all known CpG islands (CGIs) using microarray technologies. A large percentage of signals obtained from microarrays can be attributed to various measurable and unmeasurable confounding factors unrelated to the biological question at hand. In order to correct the bias due to noise, we first implemented a quantile regression model, with a quantile level equal to 75%, to identify hypermethylated CGIs in an earlier work. As a proof of concept, we applied this model to methylation microarray data generated from breast cancer cell lines. However, we were unsure whether 75% was the best quantile level for identifying hypermethylated CGIs. In this paper, we attempt to determine which quantile level should be used to identify hypermethylated CGIs and their associated genes. 相似文献106.
CC van Diemen DS Postma M Siedlinski A Blokstra HA Smit HM Boezen 《Respiratory research》2011,12(1):57
Background
An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking.Methods
We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152).Results
MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p = 0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.Conclusions
We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population. 相似文献107.
Background
Hybridization can have complex effects on evolutionary dynamics in ants because of the combination of haplodiploid sex-determination and eusociality. While hybrid non-reproductive workers have been found in a range of species, examples of gene-flow via hybrid queens and males are rare. We studied hybridization in East African army ants (Dorylus subgenus Anomma) using morphology, mitochondrial DNA sequences, and nuclear microsatellites.Results
While the mitochondrial phylogeny had a strong geographic signal, different species were not recovered as monophyletic. At our main study site at Kakamega Forest, a mitochondrial haplotype was shared between a "Dorylus molestus-like" and a "Dorylus wilverthi-like" form. This pattern is best explained by introgression following hybridization between D. molestus and D. wilverthi. Microsatellite data from workers showed that the two morphological forms correspond to two distinct genetic clusters, with a significant proportion of individuals being classified as hybrids.Conclusions
We conclude that hybridization and gene-flow between the two army ant species D. molestus and D. wilverthi has occurred, and that mating between the two forms continues to regularly produce hybrid workers. Hybridization is particularly surprising in army ants because workers have control over which males are allowed to mate with a young virgin queen inside the colony. 相似文献108.
Julieta Ramos-Elorduy José MP Moreno Adolfo I Vázquez Ivonne Landero Héctor Oliva-Rivera Víctor HM Camacho 《Journal of ethnobiology and ethnomedicine》2011,7(1):1-22
In this paper, we reported the butterflies and moths that are consumed in Mexico. We identified 67 species of Lepidoptera that are eaten principally in their larval stage in 17 states of Mexico. These species belong to 16 families: Arctiidae, Bombycidae, Castniidae, Cossidae, Geometridae, Hepialidae, Hesperiidae, Lasiocampidae, Noctuidae, Nymphalidae, Papilionidae, Pieridae, Pyralidae, Saturniidae, Sesiidae, and Sphingidae. Saturniidae, Pieridae, Noctuidae and Nymphalidae were the more species consumed with 16, 11, 9, and 8 species, respectively. The genera with the largest numbers of species were: Phassus, Phoebis, Hylesia and Spodoptera, with three species. Their local distribution, corresponding to each state of Mexico, is also presented. 相似文献
109.
Recent horizontal transfer of a mariner transposable element among and between Diptera and Neuroptera 总被引:11,自引:4,他引:7
Transposable elements of the mariner family are widespread among insects
and other invertebrates, and initial analyses of their relationships
indicated frequent occurrence of horizontal transfers between hosts. A
specific PCR assay was used to screen for additional members of the
irritans subfamily of mariners in more than 400 arthropod species.
Phylogenetic analysis of cloned PCR fragments indicated that relatively
recent horizontal transfers had occurred into the lineages of a fruit fly
Drosophila ananassae, the horn fly Haematobia irritans, the African malaria
vector mosquito Anopheles gambiae, and a green lacewing Chrysoperla
plorabunda. Genomic dot-blot analysis revealed that the copy number in
these species varies widely, from about 17,000 copies in the horn fly to
three copies in D. ananassae. Multiple copies were sequenced from genomic
clones from each of these species and four others with related elements.
These sequences confirmed the PCR results, revealing extremely similar
elements in each of these four species (greater than 88% DNA and 95% amino
acid identity). In particular, the consensus sequence of the transposase
gene of the horn fly elements differs by just two base pairs out of 1,044
from that of the lacewing elements. The mosquito lineage has diverged from
the other Diptera for over 200 Myr, and the neuropteran last shared a
common ancestor with them more than 265 Myr ago, so this high similarity
implies that these transposons recently transferred horizontally into each
lineage. Their presence in only the closest relatives in at least the
lacewing lineage supports this hypothesis. Such horizontal transfers
provide an explanation for the evolutionary persistence and widespread
distribution of mariner transposons. We propose that the ability to
transfer horizontally to new hosts before extinction by mutation in the
current host constitutes the primary selective constraint maintaining the
sequence conservation of mariners and perhaps other DNA-mediated elements.
相似文献
110.
Mohamed M Thabet Thomas WJ Huizinga Désirée M van der Heijde Annette HM van der Helm-van Mil 《Arthritis research & therapy》2009,11(5):R155