全文获取类型
收费全文 | 594篇 |
免费 | 35篇 |
出版年
2018年 | 9篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 24篇 |
2013年 | 33篇 |
2012年 | 25篇 |
2011年 | 18篇 |
2010年 | 32篇 |
2009年 | 35篇 |
2008年 | 26篇 |
2007年 | 24篇 |
2006年 | 14篇 |
2005年 | 21篇 |
2004年 | 17篇 |
2003年 | 15篇 |
2002年 | 11篇 |
2001年 | 16篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1997年 | 10篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 10篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 9篇 |
1982年 | 21篇 |
1981年 | 5篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 8篇 |
1977年 | 7篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1971年 | 4篇 |
1969年 | 4篇 |
1933年 | 3篇 |
1929年 | 3篇 |
1927年 | 3篇 |
1911年 | 3篇 |
排序方式: 共有629条查询结果,搜索用时 31 毫秒
101.
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
102.
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103.
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104.
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105.
Several investigators have observed that sodium ion enhances the binding of naloxone to opioid receptors. This effect has generally been attributed to allosteric modulation of the state of the mu receptor. However, a recent claim has been made that the enhancement does not involve a change in the mu receptor, but instead occurs because naloxone becomes a more kappa-specific drug when sodium ion is present in high concentration. Since the claim was not based on experimental evidence from binding studies involving known high-affinity kappa ligands, we have investigated the competition of naloxone for the kappa site using [3H]U-69593 as the marker for receptor binding. Assays were carried out in the presence and absence of 100 mM NaCl. The results of the study indicate that sodium ion does not increase the affinity of naloxone or U-69593 for the kappa receptor. 相似文献
106.
Li J Sun L Xu C Yu F Zhou H Zhao Y Zhang J Cai J Mao C Tang L Xu Y He J 《生物化学与生物物理学报(英文版)》2012,44(4):300-306
The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity. 相似文献
107.
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
108.
Unconventional myosins. 总被引:1,自引:0,他引:1
The unconventional myosins form a large and diverse group of molecular motors. The number of known unconventional myosins is increasing rapidly and in the past year alone two new classes have been identified. Substantial progress has been made towards characterizing the properties and functions of these motor proteins, which have been hypothesized to play fundamental roles in processes such as cell locomotion, phagocytosis and vesicle transport. 相似文献
109.
Characterization of the interaction between calpactin I and fodrin (non-erythroid spectrin) 总被引:2,自引:0,他引:2
Calpactin I, a calcium-binding protein associated with the membrane cytoskeleton, has been reported to bind to a calcium-dependent manner to fodrin, to certain phospholipids, and to F-actin. We have investigated the interaction between calpactin I and fodrin. Using a gel filtration assay, we observed one or more calpactin I molecules were bound calcium-dependently only at high concentrations of calpactin (greater than 1 microM), indicating that the interaction is of only moderate affinity. At higher concentrations of calpactin I, the calpactin coprecipitated with fodrin in a calcium-dependent manner. The molar ratio of calpactin to fodrin tetramer in the precipitate was greater than 25:1, indicating that the calpactin binds to a large number of sites. Moreover, the monomeric form of calpactin I (p36), which did not induce precipitation of fodrin, showed no evidence of saturation in its binding to fodrin even when more than 30 mol of p36 were bound per mole of fodrin tetramer. Several proteins other than fodrin, including clathrin, alpha-actinin, and neurofilament-H, also interacted calcium-dependently with calpactin I in the gel filtration assay. These results demonstrate that the interaction between calpactin and fodrin is not of high affinity, is not readily saturated, and is not specific for fodrin. Our results suggest that calpactin's interaction with fodrin is a particular example of a calcium-dependent, but promiscuous, binding of calpactin to proteins. 相似文献
110.