全文获取类型
收费全文 | 325篇 |
免费 | 17篇 |
国内免费 | 1篇 |
专业分类
343篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 22篇 |
2014年 | 23篇 |
2013年 | 29篇 |
2012年 | 33篇 |
2011年 | 29篇 |
2010年 | 27篇 |
2009年 | 16篇 |
2008年 | 15篇 |
2007年 | 20篇 |
2006年 | 12篇 |
2005年 | 18篇 |
2004年 | 16篇 |
2003年 | 14篇 |
2002年 | 10篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有343条查询结果,搜索用时 0 毫秒
51.
Reinier P Akkermans Marvin A Berrevoets Ivo J Smeele Annelies E Lucas Bart P Thoonen Joke G Grootens-Stekelenburg Yvonne F Heijdra Chris van Weel Tjard R Schermer 《BMC pulmonary medicine》2012,12(1):1-14
Background
Current COPD guidelines advocate a fixed < 0.70 FEV1/FVC cutpoint to define airflow obstruction. We compared rate of lung function decline in respiratory symptomatic 40+ subjects who were 'obstructive' or 'non-obstructive' according to the fixed and/or age and gender specific lower limit of normal (LLN) FEV1/FVC cutpoints.Methods
We studied 3,324 respiratory symptomatic subjects referred to primary care diagnostic centres for spirometry. The cohort was subdivided into four categories based on presence or absence of obstruction according to the fixed and LLN FEV1/FVC cutpoints. Postbronchodilator FEV1 decline served as primary outcome to compare subjects between the respective categories.Results
918 subjects were obstructive according to the fixed FEV1/FVC cutpoint; 389 (42%) of them were non-obstructive according to the LLN cutpoint. In smokers, postbronchodilator FEV1 decline was 21 (SE 3) ml/year in those non-obstructive according to both cutpoints, 21 (7) ml/year in those obstructive according to the fixed but not according to the LLN cutpoint, and 50 (5) ml/year in those obstructive according to both cutpoints (p = 0.004).Conclusion
This study showed that respiratory symptomatic 40+ smokers and non-smokers who show FEV1/FVC values below the fixed 0.70 cutpoint but above their age/gender specific LLN value did not show accelerated FEV1 decline, in contrast with those showing FEV1/FVC values below their LLN cutpoint. 相似文献52.
de Witte MA Jorritsma A Kaiser A van den Boom MD Dokter M Bendle GM Haanen JB Schumacher TN 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(7):5128-5136
Adoptive transfer of TCR gene-modified T cells has been proposed as an attractive approach to target tumors for which it is difficult or impossible to induce strong tumor-specific T cell responses by vaccination. Whereas the feasibility of generating tumor Ag-specific T cells by gene transfer has been demonstrated, the factors that determine the in vivo effectiveness of TCR-modified T cells are largely unknown. We have analyzed the value of a number of clinically feasible strategies to enhance the antitumor potential of TCR modified T cells. These experiments reveal three factors that contribute greatly to the in vivo potency of TCR-modified T cells. First, irradiation-induced host conditioning is superior to vaccine-induced activation of genetically modified T cells. Second, increasing TCR expression through genetic optimization of TCR sequences has a profound effect on in vivo antitumor activity. Third, a high precursor frequency of TCR modified T cells within the graft is essential. Tumors that ultimately progress in animals treated with this optimized regimen for TCR-based adoptive cell transfer invariably display a reduced expression of the target Ag. This suggests TCR gene therapy can achieve a sufficiently strong selective pressure to warrant the simultaneous targeting of multiple Ags. The strategies outlined in this study should be of value to enhance the antitumor activity of TCR-modified T cells in clinical trials. 相似文献
53.
Wei Zhang Nick Bansback Annelies Boonen Adam Young Amitabh Singh Aslam H Anis 《Arthritis research & therapy》2010,12(5):R177
Introduction
The Work Productivity and Activity Impairment (WPAI) questionnaire is a well validated instrument to measure impairments in work and activities. However, its validation among patients with rheumatoid arthritis (RA) has not been well established. The present study's purpose is to evaluate the construct validity of the WPAI-general health version among RA patients and its ability to differentiate between RA patients with varying health status. 相似文献54.
Annelies Onraedt Cassandra De Muynck Bart Walcarius Wim Soetaert Erick Vandamme 《Biotechnology letters》2005,26(19):1481-1485
As a halotolerant bacterial species, Brevibacterium epidermis DSM 20659 can grow at relatively high salinity, tolerating up to 2 m NaCl. It synthesizes ectoine and the intracellular content increases with the medium salinity, with a maximum of 0.14 g ectoine/g CDW at 1 m NaCl. Sugar-stressed cells do not synthesize ectoine. Ectoine synthesis is also affected by the presence of external osmolytes. Added betaine is taken up and completely replaced ectoine, while l-proline is only temporarily accumulated after which ectoine is synthesized. The strain can metabolize ectoine; l-glutamate is a better carbon source for ectoine synthesis than l-aspartate. 相似文献
55.
Tomasz Jaworski Ilse Dewachter Benoit Lechat Sophie Croes Annelies Termont David Demedts Peter Borghgraef Herman Devijver Robert K. Filipkowski Leszek Kaczmarek Sebastian Kügler Fred Van Leuven 《PloS one》2009,4(10)
In Alzheimer''s disease tauopathy is considered secondary to amyloid, and the duality obscures their relation and the definition of their respective contributions.Transgenic mouse models do not resolve this problem conclusively, i.e. the relative hierarchy of amyloid and tau pathology depends on the actual model and the genes expressed or inactivated. Here, we approached the problem in non-transgenic models by intracerebral injection of adeno-associated viral vectors to express protein tau or amyloid precursor protein in the hippocampus in vivo. AAV-APP mutant caused neuronal accumulation of amyloid peptides, and eventually amyloid plaques at 6 months post-injection, but with only marginal hippocampal cell-death. In contrast, AAV-Tau, either wild-type or mutant P301L, provoked dramatic degeneration of pyramidal neurons in CA1/2 and cortex within weeks. Tau-mediated neurodegeneration proceeded without formation of large fibrillar tau-aggregates or tangles, but with increased expression of cell-cycle markers.We present novel AAV-based models, which demonstrate that protein tau mediates pyramidal neurodegeneration in vivo. The data firmly support the unifying hypothesis that post-mitotic neurons are forced to re-enter the cell-cycle in primary and secondary tauopathies, including Alzheimer''s disease. 相似文献
56.
Veenma D Beurskens N Douben H Eussen B Noomen P Govaerts L Grijseels E Lequin M de Krijger R Tibboel D de Klein A Van Opstal D 《PloS one》2010,5(12):e15348
In this paper we present the detailed clinical and cytogenetic analysis of a prenatally detected complex Congenital Diaphragmatic Hernia (CDH) patient with a mosaic unbalanced translocation (5;12). High-resolution whole genome SNP array confirmed a low-level mosaicism (20%) in uncultured cells, underlining the value of array technology for identification studies. Subsequently, targeted Fluorescence In-Situ Hybridization in postmortem collected tissues demonstrated a similar low-level mosaicism, independently of the affected status of the tissue. Thus, a higher incidence of the genetic aberration in affected organs as lung and diaphragm cannot explain the severe phenotype of this complex CDH patient. Comparison with other described chromosome 5p and 12p anomalies indicated that half of the features presented in our patient (including the diaphragm defect) could be attributed to both chromosomal areas. In contrast, a few features such as the palpebral downslant, the broad nasal bridge, the micrognathia, microcephaly, abnormal dermatoglyphics and IUGR better fitted the 5p associated syndromes only. This study underlines the fact that low-level mosaicism can be associated with severe birth defects including CDH. The contribution of mosaicism to human diseases and specifically to congenital anomalies and spontaneous abortions becomes more and more accepted, although its phenotypic consequences are poorly described phenomena leading to counseling issues. Therefore, thorough follow-up of mosaic aberrations such as presented here is indicated in order to provide genetic counselors a more evidence based prediction of fetal prognosis in the future. 相似文献
57.
Eduardo Massad Annelies Wilder-Smith Raphael Ximenes Marcos Amaku Luis Fernandez Lopez Francisco Antonio Bezerra Coutinho Giovanini Evelim Coelho Jarbas Barbosa da Silva Jr Claudio José Struchiner Marcelo Nascimento Burattini 《Memórias do Instituto Oswaldo Cruz》2014,109(3):394-397
Brazil will host the FIFA World Cup™, the biggest single-event competition in the
world, from June 12-July 13 2014 in 12 cities. This event will draw an estimated
600,000 international visitors. Brazil is endemic for dengue. Hence, attendees of the
2014 event are theoretically at risk for dengue. We calculated the risk of dengue
acquisition to non-immune international travellers to Brazil, depending on the
football match schedules, considering locations and dates of such matches for June
and July 2014. We estimated the average per-capita risk and expected
number of dengue cases for each host-city and each game schedule chosen based on
reported dengue cases to the Brazilian Ministry of Health for the period between
2010-2013. On the average, the expected number of cases among the 600,000 foreigner
tourists during the World Cup is 33, varying from 3-59. Such risk estimates will not
only benefit individual travellers for adequate pre-travel preparations, but also
provide valuable information for public health professionals and policy makers
worldwide. Furthermore, estimates of dengue cases in international travellers during
the World Cup can help to anticipate the theoretical risk for exportation of dengue
into currently non-infected areas. 相似文献
58.
Phytophthora ramorum is a recently introduced pathogen in Europe and North America consisting of three clonal lineages. Due to the limited intralineage genetic variation, only a few polymorphic markers are available for use in studies involving the epidemiology and evolution of P. ramorum. A total of 159 primer pairs for candidate polymorphic SSR loci were tested with universal labeling. Four polymorphic microsatellite loci were identified within the NA1 lineage and one within the NA2 lineage, demonstrating the power and flexibility of the screening technique. The markers may significantly increase the number of genotypes that can be identified and as such can help better characterize the North American lineages of P. ramorum. 相似文献
59.
We have studied the modulation of gating properties of the Ca2+-permeable, cation channel TRPV4 transiently expressed in HEK293 cells. The phorbol ester 4alphaPDD transiently activated a current through TRPV4 in the presence of extracellular Ca2+. Increasing the concentration of extracellular Ca2+ ([Ca2+](e)) reduced the current amplitude and accelerated its decay. This decay was dramatically delayed in the absence of [Ca2+](e). It was also much slower in the presence of [Ca2+](e) in a mutant channel, obtained by a point mutation in the 6th transmembrane domain, F707A. Mutant channels, containing a single mutation in the C-terminus of TRPV4 (E797), were constitutively open. In conclusion, gating of the 4alphaPDD-activated TRPV4 channel depends on both extra- and intracellular Ca2+, and is modulated by mutations of single amino acid residues in the 6th transmembrane domain and the C-terminus of the TRPV4 protein. 相似文献
60.