全文获取类型
收费全文 | 318篇 |
免费 | 18篇 |
专业分类
336篇 |
出版年
2021年 | 3篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 11篇 |
2013年 | 13篇 |
2012年 | 21篇 |
2011年 | 9篇 |
2010年 | 14篇 |
2009年 | 10篇 |
2008年 | 22篇 |
2007年 | 20篇 |
2006年 | 14篇 |
2005年 | 15篇 |
2004年 | 15篇 |
2003年 | 21篇 |
2002年 | 36篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1980年 | 6篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1976年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有336条查询结果,搜索用时 15 毫秒
111.
Magne D Palmer G Barton JL Mézin F Talabot-Ayer D Bas S Duffy T Noger M Guerne PA Nicklin MJ Gabay C 《Arthritis research & therapy》2006,8(3):R80-11
Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8 mRNA expression was increased in hSFs upon stimulation with proinflammatory cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL-1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore, although IL-1beta protein levels were increased in inflamed human and mouse joint tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were similar to or lower than those in matched serum samples, suggesting that the joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and septic shock, and did not correlate with inflammatory status. Interestingly however, we observed high IL-1F8 levels in several serum samples in all groups. In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. It remains to be determined whether circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis. 相似文献
112.
Reybier K Boyer J Farines V Camus F Souchard JP Monje MC Bernardes-Genisson V Goldstein S Nepveu F 《Free radical research》2006,40(1):11-20
The ability of ten imidazolyl nitrones to directly scavenge free radicals (R(*)) generated in polar ((*)OH, O(*)(2)(-), SO(*)(3)(-) cysteinyl, (*)CH(3)) or in apolar (CH(3)-(*)CH-CH(3)) media has been studied. When oxygen or sulfur-centered radicals are generated in polar media, EPR spectra are not or weakly observed with simple spectral features. Strong line intensities and more complicated spectra are observed with the isopropyl radical generated in an apolar medium. Intermediate results are obtained with (*)CH(3) generated in a polar medium. EPR demonstrates the ability of these nitrones to trap radicals to the nitrone C(alpha) atom (alpha radical adduct) and to the imidazol C(5) atom (5-radical adduct). Beside the nucleophilic addition of the radical to the C(alpha) atom, the EPR studies suggest a two-step mechanism for the overall reaction of R(*) attacking the imidazol core. The two steps seem to occur very fast with the (*)OH radical obtained in a polar medium and slower with the isopropyl radical prepared in benzene. In conclusion, imidazolyl nitrones present a high capacity to trap and stabilize carbon-centered radicals. 相似文献
113.
Hubert Halimi Annafrancesca Rigato Deborah Byrne Géraldine Ferracci Corinne Sebban-Kreuzer Latifa ElAntak Francoise Guerlesquin 《PloS one》2014,9(11)
Human Galectin-3 is found in the nucleus, the cytoplasm and at the cell surface. This lectin is constituted of two domains: an unfolded N-terminal domain and a C-terminal Carbohydrate Recognition Domain (CRD). There are still uncertainties about the relationship between the quaternary structure of Galectin-3 and its carbohydrate binding properties. Two types of self-association have been described for this lectin: a C-type self-association and a N-type self-association. Herein, we have analyzed Galectin-3 oligomerization by Dynamic Light Scattering using both the recombinant CRD and the full length lectin. Our results proved that LNnT induces N-type self-association of full length Galectin-3. Moreover, from Nuclear Magnetic Resonance (NMR) and Surface Plasmon Resonance experiments, we observed no significant specificity or affinity variations for carbohydrates related to the presence of the N-terminal domain of Galectin-3. NMR mapping clearly established that the N-terminal domain interacts with the CRD. We propose that LNnT induces a release of the N-terminal domain resulting in the glycan-dependent self-association of Galectin-3 through N-terminal domain interactions. 相似文献
114.
Vγ9Vδ2 T cells play an important role in the immune response to infectious agents but the mechanisms contributing to this immune process remain to be better characterized. Following their activation, Vγ9Vδ2 T cells develop cytotoxic activity against infected cells, secrete large amounts of cytokines and influence the function of other effectors of immunity, notably cells playing a key role in the initiation of the adaptive immune response such as dendritic cells. Brucella infection dramatically impairs dendritic cell maturation and their capacity to present antigens to T cells. Herein, we investigated whether V T cells have the ability to restore the full functional capacities of Brucella-infected dendritic cells. Using an in vitro multicellular infection model, we showed that: 1/Brucella-infected dendritic cells activate Vγ9Vδ2 T cells through contact-dependent mechanisms, 2/activated Vγ9Vδ2 T cells induce full differentiation into IL-12 producing cells of Brucella-infected dendritic cells with functional antigen presentation activity. Furthermore, phosphoantigen-activated Vγ9Vδ2 T cells also play a role in triggering the maturation process of dendritic cells already infected for 24 h. This suggests that activated Vγ9Vδ2 T cells could be used to modulate the outcome of infectious diseases by promoting an adjuvant effect in dendritic cell-based cellular therapies. 相似文献
115.
Hettick JM Green BJ Buskirk AD Kashon ML Slaven JE Janotka E Blachere FM Schmechel D Beezhold DH 《Analytical biochemistry》2008,380(2):276-281
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI–TOF MS) was used to generate highly reproducible mass spectral fingerprints for 12 species of fungi of the genus Aspergillus and 5 different strains of Aspergillus flavus. Prior to MALDI–TOF MS analysis, the fungi were subjected to three 1-min bead beating cycles in an acetonitrile/trifluoroacetic acid solvent. The mass spectra contain abundant peaks in the range of 5 to 20 kDa and may be used to discriminate between species unambiguously. A discriminant analysis using all peaks from the MALDI–TOF MS data yielded error rates for classification of 0 and 18.75% for resubstitution and cross-validation methods, respectively. If a subset of 28 significant peaks is chosen, resubstitution and cross-validation error rates are 0%. Discriminant analysis of the MALDI–TOF MS data for 5 strains of A. flavus using all peaks yielded error rates for classification of 0 and 5% for resubstitution and cross-validation methods, respectively. These data indicate that MALDI–TOF MS data may be used for unambiguous identification of members of the genus Aspergillus at both the species and strain levels. 相似文献
116.
Rapid culture-based methods for drug-resistance detection in Mycobacterium tuberculosis 总被引:1,自引:0,他引:1
Tuberculosis still represents a major public health problem, especially in low-resource countries where the burden of the disease is more important. Multidrug-resistant and extensively drug drug-resistant tuberculosis constitute serious problems for the efficient control of the disease stressing the need to investigate resistance to first- and second-line drugs. Conventional methods for detecting drug-resistance in Mycobacterium tuberculosis are slow and cumbersome. The most commonly used proportion method on L?wenstein-Jensen medium or Middlebrook agar requires a minimum of 3-4 weeks to produce results. Several new approaches have been proposed in the last years for the rapid and timely detection of drug-resistance in tuberculosis. This review will address phenotypic culture-based methods for rapid drug susceptibility testing in M. tuberculosis. 相似文献
117.
Yu JK Mazet F Chen YT Huang SW Jung KC Shimeld SM 《Development genes and evolution》2008,218(11-12):629-638
118.
Fabrice Compain Nawel Aït-Ammar Françoise Botterel Laure Gibault Francoise Le Pimpec Barthes Eric Dannaoui 《Mycopathologia》2017,182(9-10):907-913
We report here a case of cavitary pneumonia due to Rhizopus homothallicus in a diabetic patient. This is the first proven case of R. homothallicus infection in Western countries and the third case described worldwide. The organism was isolated from lung biopsy and identified after amplification and sequencing of the internal transcribed spacer region. 相似文献
119.
120.
Dalmais M Schmidt J Le Signor C Moussy F Burstin J Savois V Aubert G Brunaud V de Oliveira Y Guichard C Thompson R Bendahmane A 《Genome biology》2008,9(2):R43-12
The systematic characterization of gene functions in species recalcitrant to Agrobacterium-based transformation, like Pisum sativum, remains a challenge. To develop a high throughput forward and reverse genetics tool in pea, we have constructed a reference ethylmethane sulfonate mutant population and developed a database, UTILLdb, that contains phenotypic as well as sequence information on mutant genes. UTILLdb can be searched online for TILLING alleles, through the BLAST tool, or for phenotypic information about mutants by keywords. 相似文献