全文获取类型
收费全文 | 447篇 |
免费 | 28篇 |
出版年
2022年 | 5篇 |
2021年 | 1篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 11篇 |
2015年 | 24篇 |
2014年 | 19篇 |
2013年 | 36篇 |
2012年 | 26篇 |
2011年 | 24篇 |
2010年 | 27篇 |
2009年 | 32篇 |
2008年 | 22篇 |
2007年 | 17篇 |
2006年 | 16篇 |
2005年 | 25篇 |
2004年 | 17篇 |
2003年 | 11篇 |
2002年 | 8篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 9篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 8篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 17篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有475条查询结果,搜索用时 31 毫秒
81.
JM Rodríguez-Domínguez LL Ríos-Lara E Tapia-Campos R Barba-Gonzalez 《Biotechnic & histochemistry》2017,92(3):159-166
Preparations that contain well-spread metaphase chromosomes are critical for plant cytogenetic analyses including chromosome counts, banding procedures, in situ hybridization, karyotyping and construction of ideograms. Chromosome spreading is difficult for plants with large and numerous chromosomes. We report here a technique for obtaining cytoplasm-free, well-spread metaphases from two Amaryllidaceae species: Sprekelia formosissima (2n = 120) and Hymenocallis howardii (2n = 96). The technique has three main steps: 1) pretreatment to cause chromosome condensation, 2) dripping onto tilted slides coated with a thin layer of pure acetic acid and 3) application of steam and acetic acid to produce cytoplasmic hydrolysis, which spreads the chromosomes. 相似文献
82.
Rebecca C Mueller Fabiana S Paula Babur S Mirza Jorge LM Rodrigues Klaus Nüsslein Brendan JM Bohannan 《The ISME journal》2014,8(7):1548-1550
Understanding the interactions among microbial communities, plant communities and soil properties following deforestation could provide insights into the long-term effects of land-use change on ecosystem functions, and may help identify approaches that promote the recovery of degraded sites. We combined high-throughput sequencing of fungal rDNA and molecular barcoding of plant roots to estimate fungal and plant community composition in soil sampled across a chronosequence of deforestation. We found significant effects of land-use change on fungal community composition, which was more closely correlated to plant community composition than to changes in soil properties or geographic distance, providing evidence for strong links between above- and below-ground communities in tropical forests. 相似文献
83.
Susan JM Hoonhorst Wim Timens Leo Koenderman Adèle T Lo Tam Loi Jan-Willem J Lammers H Marike Boezen Antoon JM van Oosterhout Dirkje S Postma Nick HT ten Hacken 《Respiratory research》2014,15(1)
Background
Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age.Methods
All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis.Results
Young susceptible individuals showed significantly higher increases in the expression of FcγRII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients.Conclusions
We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD.Trial registration
Clinicaltrials.gov: NCT00807469Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0121-2) contains supplementary material, which is available to authorized users. 相似文献84.
Claudia T Guimaraes Christiano C Simoes Maria Marta Pastina Lyza G Maron Jurandir V Magalhaes Renato CC Vasconcellos Lauro JM Guimaraes Ubiraci GP Lana Carlos FS Tinoco Roberto W Noda Silvia N Jardim-Belicuas Leon V Kochian Vera MC Alves Sidney N Parentoni 《BMC genomics》2014,15(1)
Background
Aluminum (Al) toxicity is an important limitation to food security in tropical and subtropical regions. High Al saturation on acid soils limits root development, reducing water and nutrient uptake. In addition to naturally occurring acid soils, agricultural practices may decrease soil pH, leading to yield losses due to Al toxicity. Elucidating the genetic and molecular mechanisms underlying maize Al tolerance is expected to accelerate the development of Al-tolerant cultivars.Results
Five genomic regions were significantly associated with Al tolerance, using 54,455 SNP markers in a recombinant inbred line population derived from Cateto Al237. Candidate genes co-localized with Al tolerance QTLs were further investigated. Near-isogenic lines (NILs) developed for ZmMATE2 were as Al-sensitive as the recurrent line, indicating that this candidate gene was not responsible for the Al tolerance QTL on chromosome 5, qALT5. However, ZmNrat1, a maize homolog to OsNrat1, which encodes an Al3+ specific transporter previously implicated in rice Al tolerance, was mapped at ~40 Mbp from qALT5. We demonstrate for the first time that ZmNrat1 is preferentially expressed in maize root tips and is up-regulated by Al, similarly to OsNrat1 in rice, suggesting a role of this gene in maize Al tolerance. The strongest-effect QTL was mapped on chromosome 6 (qALT6), within a 0.5 Mbp region where three copies of the Al tolerance gene, ZmMATE1, were found in tandem configuration. qALT6 was shown to increase Al tolerance in maize; the qALT6-NILs carrying three copies of ZmMATE1 exhibited a two-fold increase in Al tolerance, and higher expression of ZmMATE1 compared to the Al sensitive recurrent parent. Interestingly, a new source of Al tolerance via ZmMATE1 was identified in a Brazilian elite line that showed high expression of ZmMATE1 but carries a single copy of ZmMATE1.Conclusions
High ZmMATE1 expression, controlled either by three copies of the target gene or by an unknown molecular mechanism, is responsible for Al tolerance mediated by qALT6. As Al tolerant alleles at qALT6 are rare in maize, marker-assisted introgression of this QTL is an important strategy to improve maize adaptation to acid soils worldwide.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-153) contains supplementary material, which is available to authorized users. 相似文献85.
Rachel Knevel Diederik PC de Rooy Tore Saxne Elisabet Lindqvist Martha K Leijsma Nina A Daha Bobby PC Koeleman Roula Tsonaka Jeanine J Houwing-Duistermaat Joris JM Schonkeren Rene EM Toes Tom WJ Huizinga Elisabeth Brouwer Anthony G Wilson Annette HM van der Helm-van Mil 《Arthritis research & therapy》2014,16(3):R108
Introduction
Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA.Methods
1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied.Results
We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10−4). This variant was also significant after Bonferroni correction.Conclusions
These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA. 相似文献86.
Oriol Vall Mario Gomez-Culebras Carme Puig Ernesto Rodriguez-Carrasco Arelis Gomez Baltazar Lizzeth Canchucaja Xavier Joya Oscar Garcia-Algar 《PloS one》2014,9(1)
Introduction
The use of p,p′-dichlorodiphenyltrichloroethane (DDT) has been banned since the late 1970s due to its toxicity. However, its long half-life makes it persistent in the environment and, consequently, almost everyone has DDT residues in the body. Human milk constitutes an ideal non-conventional matrix to investigate environmental chronic exposure to organochlorine compounds (OCs) residues. The study aimed to identify potential population risk factors of exposure to DDT due to the proximity to countries where it is still used.Methods
Seventy-two consecutive lactating women were prospectively included in Tenerife, Canary Islands (Spain). A validated questionnaire was used to obtain socioeconomic, demographics data, and daily habits during pregnancy. DDT levels in breast milk were measured by gas chromatography with-electron capture detector (GC-ECD). Anthropometrics measurements in newborns were obtained.Results
Thirty-four out of 72 (47.2%) of the analysed milk samples presented detectable levels of DDT (mean: 0.92 ng/g), ranging between 0.08 to 16.96 ng/g. The socio-demographic variables did not significantly differ between detectable DDT and non-detectable DDT groups. We found positive association between DDT levels and vegetables (OR (95%CI): 1.23 (1.01–1.50)) and poultry meat (OR (95%CI): 2.05 (1.16–3.60)) consumption, and also between the presence of DDT in breast milk and gestational age (OR (95%CI): 0.59 (0.40–0.90)).Conclusions
DDT is present in breast milk of women at the time of delivery. Residual levels and the spread from countries still using DDT explain DDT detection from vegetables and from animal origin food. The presence of this compound in breast milk represents a pre- and postnatal exposure hazard for foetuses and infants due to chronic bioaccumulation and poor elimination, with possible deleterious effects on health. This data should be used to raise awareness of the risks of OCs exposure and to help establish health policies in order to avoid its use worldwide and thus, to prevent its propagation. 相似文献87.
Marta L. Silva Baltazar C Nuno S. Osrio Pedro N. S. Rodrigues Ana Raquel Maceiras Margarida Saraiva 《PLoS pathogens》2022,18(5)
Tuberculosis (TB), one of the deadliest threats to human health, is mainly caused by 2 highly related and human-adapted bacteria broadly known as Mycobacterium tuberculosis and Mycobacterium africanum. Whereas M. tuberculosis is widely spread, M. africanum is restricted to West Africa, where it remains a significant cause of tuberculosis. Although several differences have been identified between these 2 pathogens, M. africanum remains a lot less studied than M. tuberculosis. Here, we discuss the genetic, phenotypic, and clinical similarities and differences between strains of M. tuberculosis and M. africanum. We also discuss our current knowledge on the immune response to M. africanum and how it possibly articulates with distinct disease progression and with the geographical restriction attributed to this pathogen. Understanding the functional impact of the diversity existing in TB-causing bacteria, as well as incorporating this diversity in TB research, will contribute to the development of better, more specific approaches to tackle TB. 相似文献
88.
The signal produced by fluorescence in situ hybridization (FISH) often is inconsistent among cells and sensitivity is low. Small DNA targets on the chromatin are difficult to detect. We report here an improved nick translation procedure for Texas red and Alexa Fluor 488 direct labeling of FISH probes. Brighter probes can be obtained by adding excess DNA polymerase I. Using such probes, a 30 kb yeast transgene, and the rp1, rp3 and zein multigene clusters were clearly detected. 相似文献
89.
90.
18S rRNA data indicate that Aschelminthes are polyphyletic in origin and consist of at least three distinct clades 总被引:7,自引:1,他引:6
Winnepenninckx B; Backeljau T; Mackey LY; Brooks JM; De Wachter R; Kumar S; Garey JR 《Molecular biology and evolution》1995,12(6):1132-1137
The Aschelminthes is a collection of at least eight animal phyla,
historically grouped together because the absence of a true body cavity was
perceived as a pseudocoelom. Analyses of 18S rRNA sequences from six
Aschelminth phyla (including four previously unpublished sequences) support
polyphyly for the Aschelminthes. At least three distinct groups of
Aschelminthes were detected: the Priapulida among the protostomes, the
Rotifera-Acanthocephala as a sister group to the protostomes, and the
Nematoda as a basal group to the triploblastic Eumetazoa.
相似文献