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131.
Jo?o Perdig?o Hugo Silva Diana Machado Rita Macedo Fernando Maltez Carla Silva Luisa Jordao Isabel Couto Kim Mallard Francesc Coll Grant A Hill-Cawthorne Ruth McNerney Arnab Pain Taane G Clark Miguel Viveiros Isabel Portugal 《BMC genomics》2014,15(1)
Background
Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades.Results
In the present study we have genotyped and sequenced the genomes of 56 Mycobacterium tuberculosis isolates recovered mostly from Lisbon. The genotyping data revealed three major clusters associated with MDR-TB, two of which are associated with XDR-TB. Whilst the genomic data contributed to elucidate the phylogenetic positioning of circulating MDR-TB strains, showing a high predominance of a single SNP cluster group 5. Furthermore, a genome-wide phylogeny analysis from these strains, together with 19 publicly available genomes of Mycobacterium tuberculosis clinical isolates, revealed two major clades responsible for M/XDR-TB in the region: Lisboa3 and Q1 (LAM).The data presented by this study yielded insights on microevolution and identification of novel compensatory mutations associated with rifampicin resistance in rpoB and rpoC. The screening for other structural variations revealed putative clade-defining variants. One deletion in PPE41, found among Lisboa3 isolates, is proposed to contribute to immune evasion and as a selective advantage. Insertion sequence (IS) mapping has also demonstrated the role of IS6110 as a major driver in mycobacterial evolution by affecting gene integrity and regulation.Conclusions
Globally, this study contributes with novel genome-wide phylogenetic data and has led to the identification of new genomic variants that support the notion of a growing genomic diversity facing both setting and host adaptation.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-991) contains supplementary material, which is available to authorized users. 相似文献132.
Paulo C Carvalho Juliana SG Fischer Emily I Chen Gilberto B Domont Maria GC Carvalho Wim M Degrave John R Yates III Valmir C Barbosa 《Proteome science》2009,7(1):6-11
Background
Spectral counting is a shotgun proteomics approach comprising the identification and relative quantitation of thousands of proteins in complex mixtures. However, this strategy generates bewildering amounts of data whose biological interpretation is a challenge. 相似文献133.
As high-throughput genomic tools, such as the DNA microarray platform, have lead to the development of novel genotyping procedures, such as Diversity Arrays Technology (DArT) and Single Nucleotide Polymorphisms (SNPs), it is likely that, in the future, high density linkage maps will be constructed from both dominant and co-dominant markers. Recently, a strictly genetic approach was described for estimating recombination frequency (r) between co-dominant markers in full-sib families. The complete set of maximum likelihood estimators for r in full-sib families was almost obtained, but unfortunately, one particular configuration involving dominant markers, segregating in a 3:1 ratio and co-dominant markers, was not considered. Here we add nine further estimators to the previously published set, thereby making it possible to cover all combinations of molecular markers with two to four alleles (without epistasis) in a full-sib family. This includes segregation in one or both parents, dominance and all linkage phase configurations. 相似文献
134.
Elena Deligianni Sally Pattison Daniel Berrar Nigel G Ternan Richard W Haylock John E Moore Stuart J Elborn James SG Dooley 《BMC microbiology》2010,10(1):38
Background
Pseudomonas aeruginosa is considered to grow in a biofilm in cystic fibrosis (CF) chronic lung infections. Bacterial cell motility is one of the main factors that have been connected with P. aeruginosa adherence to both biotic and abiotic surfaces. In this investigation, we employed molecular and microscopic methods to determine the presence or absence of motility in P. aeruginosa CF isolates, and statistically correlated this with their biofilm forming ability in vitro. 相似文献135.
Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-interacting protein 总被引:3,自引:0,他引:3
Chen J Couto FM Minn AH Shalev A 《Biochemical and biophysical research communications》2006,346(3):1067-1074
Exenatide (Ex-4) is a novel anti-diabetic drug that stimulates insulin secretion and enhances beta-cell mass, but the mechanisms involved are not fully understood. We found that Ex-4 protects INS-1 beta-cells against oxidative stress-induced apoptosis (TUNEL) and also reduces expression (mRNA and protein) of thioredoxin-interacting protein (TXNIP), a pro-apoptotic factor involved in beta-cell glucose toxicity and oxidative stress. This reduction was observed in INS-1 cells, mouse, and human islets as well as in wild-type mice receiving Ex-4 and was accompanied by decreased expression of the apoptotic factors caspase-3 and Bax. To determine whether Ex-4-mediated TXNIP reduction is critical for this inhibition of apoptosis, we stably overexpressed TXNIP in INS-1 cells, which completely blunted the anti-apoptotic Ex-4 effects. Thus, Ex-4 inhibits apoptosis by reducing TXNIP expression and early initiation of Ex-4 treatment may help preserve endogenous beta-cell mass, protect against oxidative stress, and delay type 2 diabetes progression. 相似文献
136.
Lopez-Larrea C Blanco-Gelaz MA Torre-Alonso JC Bruges Armas J Suarez-Alvarez B Pruneda L Couto AR Gonzalez S Lopez-Vázquez A Martinez-Borra J 《Arthritis research & therapy》2006,8(4):R101-5
Killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) loci are both highly polymorphic, and some
HLA class I molecules bind and trigger cell-surface receptors specified by KIR genes. We examined whether the combination of KIR3DS1/3DL1 genes in concert with HLA-B27 genotypes is associated with susceptibility to ankylosing spondylitis (AS). Two HLA-B27-positive
Caucasian populations were selected, one from Spain (71 patients and 105 controls) and another from the Azores (Portugal)
(55 patients and 75 controls). All were typed for HLA-B and KIR (3DS1 and 3DL1) genes. Our results show that in addition to B27, the allele 3DS1 is associated with AS compared with B27 controls (p < 0.0001 and p < 0.003 in the Spanish population and Azoreans, respectively). We also observed that the association of KIR3DS1 to AS was
found in combination with HLA-B alleles carrying Bw4-I80 in trans position in the Spanish population (30.9% in AS versus 15.2%
in B27 controls, p = 0.02, odds ratio (OR) = 2.49) and in Azoreans (27.2% in AS versus 8.7% in B27 controls, p = 0.01, OR = 4.4 in Azoreans). On the other hand, 3DL1 was decreased in patients compared with B27 controls (p < 0.0001 in the Spanish population and p < 0.003 in Azoreans). The presence of this allele in combination with Bw4-I80 had a protective effect against the development
of AS in the Spanish population (19.7% in AS, 35.2% in B27 controls; p = 0.03, OR = 0.45). The presence of KIR3DS1 or KIR3DL1 in combination with HLA-B*27s/HLA-B Bw4-I80 genotypes may modulate the development of AS. The susceptibility to AS could
be determined by the overall balance of activating and inhibitory composite KIR-HLA genotypes. 相似文献
137.
S. Rodríguez Couto D. Moldes Mª A. Sanromán 《World journal of microbiology & biotechnology》2006,22(6):607-612
Summary In the present work, the two main factors affecting enzymatic stability, i.e. pH and temperature, were analysed in order to
determine the optimum ones to maintain ligninase (LiP) and manganese-dependent peroxidase (MnP) activities for prolonged periods
of time. The optimum pH and temperature range obtained was around 4.2 and 34 °C for the former and 4.5 and 32 °C for the latter.
Under these conditions LiP and MnP showed a half-life time of about 100 and 500 h, respectively. In addition, extracellular
liquid containing mainly MnP (200 U/l) was able to decolorize about 20% of the polymeric dye Poly R-478 in 15 min. The decolorization
was carried out at a pH of 4.5 (6 mM sodium malonate) and a temperature of 30 °C. 相似文献
138.
Yanlan Yu Pierre Lee Yaohuang Ke Yongke Zhang Qiu Yu Jonathan Lee Mingzhen Li Jialiang Song Jungang Chen Jihong Dai Fernando Jose Rebelo Do Couto Zhiqiang An Weimin Zhu Guo-Liang Yu 《PloS one》2010,5(2)
Rabbit antibodies have been widely used in research and diagnostics due to their high antigen specificity and affinity. Though these properties are also highly desirable for therapeutic applications, rabbit antibodies have remained untapped for human disease therapy. To evaluate the therapeutic potential of rabbit monoclonal antibodies (RabMAbs), we generated a panel of neutralizing RabMAbs against human vascular endothelial growth factor-A (VEGF). These neutralizing RabMAbs are specific to VEGF and do not cross-react to other members of the VEGF protein family. Guided by sequence and lineage analysis of a panel of neutralizing RabMAbs, we humanized the lead candidate by substituting non-critical residues with human residues within both the frameworks and the CDR regions. We showed that the humanized RabMAb retained its parental biological properties and showed potent inhibition of the growth of H460 lung carcinoma and A673 rhabdomyosarcoma xenografts in mice. These studies provide proof of principle for the feasibility of developing humanized RabMAbs as therapeutics. 相似文献
139.
Ana Henriques Luís Inês Maura Couto Catarina Santos Paulo Santos Anabela Almeida Paula Laranjeira Maria Luísa Pais Artur Paiva 《Cellular immunology》2010,264(1):97-103
To compare frequency and functional activity of peripheral blood (PB) Th(c)17, Th(c)1 and Treg cells and the amount of type 2 cytokines mRNA we recruited SLE patients in active (n = 15) and inactive disease (n = 19) and healthy age- and gender-matched controls (n = 15). The study of Th(c)17, Th(c)1 and Treg cells was done by flow cytometry and cytokine mRNA by real-time PCR. Compared to NC, SLE patients present an increased proportion of Th(c)17 cells, but with lower amounts of IL-17 per cell and also a decreased frequency of Treg, but with increased production of TGF-β and FoxP3 mRNA. Ιn active compared to inactive SLE, there is a marked decreased in frequency of Th(c)1 cells, an increased production of type 2 cytokines mRNA and a distinct functional profile of Th(c)17 cells. Our findings suggest a functional disequilibrium of T-cell subsets in SLE which may contribute to the inflammatory process and disease pathogenesis. 相似文献