全文获取类型
收费全文 | 132篇 |
免费 | 14篇 |
出版年
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 12篇 |
2014年 | 10篇 |
2013年 | 6篇 |
2012年 | 7篇 |
2011年 | 3篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2007年 | 2篇 |
2006年 | 4篇 |
2005年 | 9篇 |
2004年 | 1篇 |
2002年 | 3篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
1934年 | 1篇 |
1932年 | 1篇 |
1931年 | 1篇 |
1928年 | 1篇 |
1926年 | 1篇 |
1923年 | 1篇 |
1903年 | 1篇 |
1900年 | 1篇 |
排序方式: 共有146条查询结果,搜索用时 15 毫秒
81.
82.
Background
Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood.This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation.Methods
Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand.Results
MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P < 0.01). TIMP-1 levels decreased from 3.5 μg/g [0.6 to 7.8] to 1.5 μg/g [0.3 to 4.9] (P = 0.16). MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05). Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05). Macrophage numbers remained level. MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01).Conclusion
During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline. 相似文献83.
Cumberbatch M Clelland K Dearman RJ Kimber I 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(1):43-50
Prolonged topical exposure of BALB/c mice to chemical contact and respiratory allergens stimulates, respectively, preferential Th1- and Th2-type responses with respect to serum Ab isotype and cytokine secretion phenotypes displayed by draining lymph node cells. We now report that differential cytokine secretion patterns are induced rapidly in the skin following first exposure to the contact allergen 2,4-dinitrochlorobenzene (DNCB) and the respiratory sensitizer trimellitic anhydride (TMA). TMA induced early expression of IL-10, a cytokine implicated in the negative regulation of Langerhans cell (LC) migration, whereas exposure to DNCB resulted in production of the proinflammatory cytokine IL-1beta. Associated with this, TMA provoked LC migration with delayed kinetics compared with DNCB, and local neutralization of IL-10 caused enhanced LC mobilization in response to TMA with concomitant up-regulation of cutaneous IL-1beta. We hypothesize that these differential epidermal cytokine profiles contribute to the polarization of immune responses to chemical allergens via effects on the phenotype of activated dendritic cells arriving in the draining lymph node. Thus, TMA-exposed dendritic cells that have been conditioned in vivo with IL-10 (a potent inhibitor of the type 1-polarizing cytokine IL-12) are effective APCs for the development of a Th2-type response. 相似文献
84.
TE Willnow C Antignac AW Br?ndli EI Christensen RD Cox D Davidson JA Davies O Devuyst G Eichele ND Hastie PJ Verroust A Schedl IC Meij 《Organogenesis》2005,2(2):42-47
Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics 相似文献
85.
In order to reconstruct phylogenetic trees from extremely dissimilar
sequences it is necessary to estimate accurately the extent of sequence
divergence. In this paper a new method of sequence analysis, Markov triple
analysis, is developed for determining the relative frequencies of
nucleotide substitutions within the three branches of a three-taxon
dendrogram. Assuming that nucleotide sites are independently and
identically distributed and assuming a Markov model for nucleotide (or
protein) evolution, it is shown that the unique Markov matrices can be
reconstructed given only the joint probability distribution relating three
taxa. (In the much simpler case involving only two taxa and two character
states, Markov matrices can also be reconstructed, provided symmetry
assumptions are placed on the elements of the matrices.) The method is
illustrated using sequence data from the combined first and second codon
positions derived from complete human, mouse, and cow mitochondrial
sequences.
相似文献
86.
DNA hybridization evidence for the principal lineages of hummingbirds (Aves:Trochilidae) 总被引:3,自引:0,他引:3
The spectacular evolutionary radiation of hummingbirds (Trochilidae) has
served as a model system for many biological studies. To begin to provide a
historical context for these investigations, we generated a complete matrix
of DNA hybridization distances among 26 hummingbirds and an outgroup swift
(Chaetura pelagica) to determine the principal hummingbird lineages. FITCH
topologies estimated from symmetrized delta TmH-C values and subjected to
various validation methods (bootstrapping, weighted jackknifing, branch
length significance) indicated a fundamental split between hermit
(Eutoxeres aquila, Threnetes ruckeri; Phaethornithinae) and nonhermit
(Trochilinae) hummingbirds, and provided strong support for six principal
nonhermit clades with the following branching order: (1) a predominantly
lowland group comprising caribs (Eulampis holosericeus) and relatives
(Androdon aequatorialis and Heliothryx barroti) with violet-ears (Colibri
coruscans) and relatives (Doryfera ludovicae); (2) an Andean-associated
clade of highly polytypic taxa (Eriocnemis, Heliodoxa, and Coeligena); (3)
a second endemic Andean clade (Oreotrochilus chimborazo, Aglaiocercus
coelestis, and Lesbia victoriae) paired with thorntails (Popelairia
conversii); (4) emeralds and relatives (Chlorostilbon mellisugus, Amazilia
tzacatl, Thalurania colombica, Orthorhyncus cristatus and Campylopterus
villaviscensio); (5) mountain-gems (Lampornis clemenciae and Eugenes
fulgens); and (6) tiny bee-like forms (Archilochus colubris, Myrtis fanny,
Acestrura mulsant, and Philodice mitchellii). Corresponding analyses on a
matrix of unsymmetrized delta values gave similar support for these
relationships except that the branching order of the two Andean clades (2,
3 above) was unresolved. In general, subsidiary relationships were
consistent and well supported by both matrices, sometimes revealing
surprising associations between forms that differ dramatically in plumage
and bill morphology. Our results also reveal some basic aspects of
hummingbird ecologic and morphologic evolution. For example, most of the
diverse endemic Andean assemblage apparently comprises two genetically
divergent clades, whereas the majority of North American hummingbirds
belong a single third clade. Genetic distances separating some
morphologically distinct genera (Oreotrochilus, Aglaiocercus, Lesbia;
Myrtis, Acestrura, Philodice) were no greater than among congeneric
(Coeligena) species, indicating that, in hummingbirds, morphological
divergence does not necessarily reflect level of genetic divergence.
相似文献
87.
88.
89.
Despite their remoteness from sources of atmospheric pollutant emissions, the Afromontane tarns in the Maloti-Drakensberg region are perfect candidates to study the negative effects of acidifying atmospheric pollution, because mountain lakes are widely recognised as sentinel ecosystems, unimpacted by direct human disturbance within their catchments. Thirty-four tarns were sampled in the Maloti-Drakensberg region and most were found to be extremely sensitive to acidic deposition, as indicated by their low acid neutralising capacity. There are very few studies of freshwater critical loads for any region within South Africa. The steady-state water chemistry model (SSWC) was adapted and used to determine critical loads, whereas exceedance was estimated relative to modelled regional deposition data, in order to understand the risk of harmful effects to aquatic ecosystems. Seventy-six percent of sampled sites across the Maloti-Drakensberg would exceed critical loads even at the lowest modelled deposition levels, but there are no current measured deposition data for the region. The sensitivity of the Maloti-Drakensberg tarns needs to be considered in future policy formulation regarding acceptable levels of acidifying atmospheric pollution from South Africa’s energy sector and indicates the need for assessing aquatic ecosystem impacts in other regions of South Africa. 相似文献
90.
I Prieto-Potín JA Roman-Blas MJ Martínez-Calatrava R Gómez R Largo Gabriel Herrero-Beaumont 《Arthritis research & therapy》2013,15(4):R81