全文获取类型
收费全文 | 961篇 |
免费 | 58篇 |
专业分类
1019篇 |
出版年
2023年 | 9篇 |
2022年 | 9篇 |
2021年 | 29篇 |
2020年 | 19篇 |
2019年 | 20篇 |
2018年 | 19篇 |
2017年 | 16篇 |
2016年 | 31篇 |
2015年 | 34篇 |
2014年 | 62篇 |
2013年 | 73篇 |
2012年 | 87篇 |
2011年 | 67篇 |
2010年 | 46篇 |
2009年 | 45篇 |
2008年 | 49篇 |
2007年 | 59篇 |
2006年 | 48篇 |
2005年 | 45篇 |
2004年 | 57篇 |
2003年 | 36篇 |
2002年 | 36篇 |
2001年 | 11篇 |
2000年 | 16篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 10篇 |
1991年 | 8篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1969年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1958年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有1019条查询结果,搜索用时 0 毫秒
41.
Lucy A. Parker Noemí GómezSaez Blanca Lumbreras Miquel Porta Ildefonso Hernández-Aguado 《PloS one》2010,5(7)
Background
QUADOMICS is an adaptation of QUADAS (a quality assessment tool for use in systematic reviews of diagnostic accuracy studies), which takes into account the particular challenges presented by ‘-omics’ based technologies. Our primary objective was to evaluate the applicability and consistency of QUADOMICS. Subsequently we evaluated and describe the methodological quality of a sample of recently published studies using the tool.Methodology/Principal Findings
45‘-omics’- based diagnostic studies were identified by systematic search of Pubmed using suitable MeSH terms (“Genomics”, “Sensitivity and specificity”, “Diagnosis”). Three investigators independently assessed the quality of the articles using QUADOMICS and met to compare observations and generate a consensus. Consistency and applicability was assessed by comparing each reviewer''s original rating with the consensus. Methodological quality was described using the consensus rating. Agreement was above 80% for all three reviewers. Four items presented difficulties with application, mostly due to the lack of a clearly defined gold standard. Methodological quality of our sample was poor; studies met roughly half of the applied criteria (mean ± sd, 54.7±18.4%). Few studies were carried out in a population that mirrored the clinical situation in which the test would be used in practice, (6, 13.3%); none described patient recruitment sufficiently; and less than half described clinical and physiological factors that might influence the biomarker profile (20, 44.4%).Conclusions
The QUADOMICS tool can consistently be applied to diagnostic ‘-omics’ studies presently published in biomedical journals. A substantial proportion of reports in this research field fail to address design issues that are fundamental to make inferences relevant for patient care. 相似文献42.
43.
Barbara G Schneider M Blanca Piazuelo Liviu A Sicinschi Robertino Mera Dun-Fa Peng Juan Carlos Roa Judith Romero-Gallo Alberto G Delgado Thibaut de Sablet Luis E Bravo Keith T Wilson Wael El-Rifai Richard M Peek Jr Pelayo Correa 《Epigenetics》2013,8(11):1153-1161
DNA methylation changes are known to occur in gastric cancers and in premalignant lesions of the gastric mucosae. In order to examine variables associated with methylation levels, we quantitatively evaluated DNA methylation in tumors, non-tumor gastric mucosae, and in gastric biopsies at promoters of 5 genes with methylation alterations that discriminate gastric cancers from non-tumor epithelia (EN1, PCDH10, RSPO2, ZIC1, and ZNF610). Among Colombian subjects at high and low risk for gastric cancer, biopsies from subjects from the high-risk region had significantly higher levels of methylation at these 5 genes than samples from subjects in the low risk region (p ≤ 0.003). When results were stratified by Helicobacter pylori infection status, infection with a cagA positive, vacA s1m1 strain was significantly associated with highest methylation levels, compared with other strains (p = 0.024 to 0.001). More severe gastric inflammation and more advanced precancerous lesions were also associated with higher levels of DNA methylation (p ≤ 0.001). In a multivariate model, location of residence of the subject and the presence of cagA and vacA s1m1 in the H. pylori strain were independent variables associated with higher methylation in all 5 genes. High levels of mononuclear cell infiltration were significantly related to methylation in PCDH10, RSPO2, and ZIC1 genes. These results indicate that for these genes, levels of methylation in precancerous lesions are related to H. pylori virulence, geographic region and measures of chronic inflammation. These genes seem predisposed to sustain significant quantitative changes in DNA methylation at early stages of the gastric precancerous process. 相似文献
44.
Shevelev I Blanca G Villani G Ramadan K Spadari S Hübscher U Maga G 《Nucleic acids research》2003,31(23):6916-6925
DNA polymerase (pol) λ is homologous to pol β and has intrinsic polymerase and terminal transferase activities. However, nothing is known about the amino acid residues involved in these activites. In order to precisely define the nucleotide-binding site of human pol λ, we have mutagenised two amino acids, Tyr505 and the neighbouring Phe506, which were predicted by structural homology modelling to correspond to the Tyr271 and Phe272 residues of pol β, which are involved in nucleotide binding. Our analysis demonstrated that pol λ Phe506Arg/Gly mutants possess very low polymerase and terminal transferase activities as well as greatly reduced abilities for processive DNA synthesis and for carrying on translesion synthesis past an abasic site. The Tyr505Ala mutant, on the other hand, showed an altered nucleotide binding selectivity to perform the terminal transferase activity. Our results suggest the existence of a common nucleotide-binding site for the polymerase and terminal transferase activities of pol λ, as well as distinct roles of the amino acids Tyr505 and Phe506 in these two catalytic functions. 相似文献
45.
Davis FJ Gupta M Camoretti-Mercado B Schwartz RJ Gupta MP 《The Journal of biological chemistry》2003,278(22):20047-20058
46.
47.
Differential ability of genotypes of 2,4-diacetylphloroglucinol-producing Pseudomonas fluorescens strains to colonize the roots of pea plants 总被引:3,自引:0,他引:3
Landa BB Mavrodi OV Raaijmakers JM McSpadden Gardener BB Thomashow LS Weller DM 《Applied and environmental microbiology》2002,68(7):3226-3237
Indigenous populations of 2,4-diacetylphloroglucinol (2,4-DAPG)-producing fluorescent Pseudomonas spp. that occur naturally in suppressive soils are an enormous resource for improving biological control of plant diseases. Over 300 isolates of 2,4-DAPG-producing fluorescent Pseudomonas spp. were isolated from the rhizosphere of pea plants grown in soils that had undergone pea or wheat monoculture and were suppressive to Fusarium wilt or take-all, respectively. Representatives of seven genotypes, A, D, E, L, O, P, and Q, were isolated from both soils and identified by whole-cell repetitive sequence-based PCR (rep-PCR) with the BOXA1R primer, increasing by three (O, P, and Q) the number of genotypes identified previously among a worldwide collection of 2,4-DAPG producers. Fourteen isolates representing eight different genotypes were tested for their ability to colonize the rhizosphere of pea plants. Population densities of strains belonging to genotypes D and P were significantly greater than the densities of other genotypes and remained above log 6.0 CFU (g of root)(-1) over the entire 15-week experiment. Genetic profiles generated by rep-PCR or restriction fragment length polymorphism analysis of the 2,4-DAPG biosynthetic gene phlD were predictive of the rhizosphere competence of the introduced 2,4-DAPG-producing strains. 相似文献
48.
Olamendi-Portugal T García BI López-González I Van Der Walt J Dyason K Ulens C Tytgat J Felix R Darszon A Possani LD 《Biochemical and biophysical research communications》2002,299(4):562-568
This report describes the isolation, primary structure determination, and functional characterization of two similar toxins from the scorpion Parabuthus granulatus named kurtoxin-like I and II (KLI and KLII, respectively). KLII from P. granulatus is identical to kurtoxin from Parabuthus transvaalicus (a 63 amino-acid long toxin) whereas KLI is a new peptide containing 62 amino acid residues closely packed by four disulfide bridges with a molecular mass of 7244. Functional assays showed that both toxins, KLI and kurtoxin from P. granulatus, potently inhibit native voltage-gated T-type Ca(2+) channel activity in mouse male germ cells. In addition, KLI was shown to significantly affect the gating mechanisms of recombinant Na(+) channels and weakly block alpha(1)3.3Ca(V) channels expressed in Xenopus oocytes. KLI and kurtoxin from P. granulatus represent new probes to study the role of ion channels in germ cells, as well as in cardiac and neural tissue. 相似文献
49.
Zanetti ME Terrile MC Arce D Godoy AV Segundo BS Casalongué C 《Journal of experimental botany》2002,53(379):2455-2457
1-Aminocyclopropane-1-carboxylate (ACC) oxidase enzyme catalyses the final step in ethylene biosynthesis, converting 1-aminocyclopropane-1-carboxylic acid to ethylene. A cDNA clone encoding an ACC oxidase, ST-ACO3, was isolated from potato (Solanum tuberosum L.) by differential screening of a Fusarium eumartii infected-tuber cDNA library. The deduced amino acid sequence exhibited similarity to other ACC oxidase proteins from several plants species. Northern blot analysis revealed that the ST-ACO3 mRNA level increased in potato tubers upon inoculation with F. eumartii, as well as after treatment with salicylic acid and indole-3-acetic acid, suggesting a cross-talk between different signalling pathways involved in the defence response of potato tubers against F. eumartii attack. 相似文献
50.
Sánchez-Sancho F Perez-Inestrosa E Suau R Montañez MI Mayorga C Torres MJ Romano A Blanca M 《Journal of molecular recognition : JMR》2003,16(3):148-156
Lack of knowledge of the exact chemical structure of cephalosporin antigenic determinants has hindered clinical interpretation of adverse reactions to these drugs and delayed understanding of the mechanisms involved in the specific recognition and binding of IgE molecules to these antigenic determinants. We further resolve the relationship between structure and activity of proposed antigenic chemicals, including the rational design and synthesis of these haptenic structures. Comparative RAST inhibition studies of the synthesized molecules revealed that they were recognized by IgE antibodies induced by cephalosporin antibiotics. Thus, these data indicate that recognition is mainly directed to the acyl side chain and to the beta-lactam fragment that remains linked to the carrier protein in the cephalosporin conjugation course. 相似文献