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81.
The soluble C-type lectin surfactant protein (SP)-A mediates lung immune responses partially via its direct effects on alveolar macrophages (AM), the main resident leukocytes exposed to antigens. SP-A modulates the AM threshold of lipopolysaccharide (LPS) activity towards an anti-inflammatory phenotype both in vitro and in vivo through various mechanisms. LPS responses are tightly regulated via distinct pathways including subcellular TLR4 localization and thus ligand sensing. The cytosolic scaffold and signaling protein β-arrestin 2 acts as negative regulator of LPS-induced TLR4 activation. Here we show that SP-A neither increases TLR4 abundancy nor co-localizes with TLR4 in primary AM. SP-A significantly reduces the LPS-induced co-localization of TLR4 with the early endosome antigen (EEA) 1 by promoting the co-localization of TLR4 with the post-Golgi compartment marker Vti1b in freshly isolated AM from rats and wild-type (WT) mice, but not in β-arrestin 2−/− AM. Compared to WT mice pulmonary LPS-induced TNF-α release in β-arrestin 2−/− mice is accelerated and enhanced and exogenous SP-A fails to inhibit both lung LPS-induced TNF-α release and TLR4/EEA1 positioning. SP-A, but not LPS, enhances β-arrestin 2 protein expression in a time-dependent manner in primary rat AM. The constitutive expression of β-arrestin 2 in AM from SP-A−/− mice is significantly reduced compared to SP-A+/+ mice and is rescued by SP-A. Prolonged endosome retention of LPS-induced TLR4 in AM from SP-A−/− mice is restored by exogenous SP-A, and is antagonized by β-arrestin 2 blocking peptides. LPS induces β-arrestin 2/TLR4 association in primary AM which is further enhanced by SP-A. The data demonstrate that SP-A modulates LPS-induced TLR4 trafficking and signaling in vitro and in vivo engaging β-arrestin 2. 相似文献
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Nijland R Lindner C van Hartskamp M Hamoen LW Kuipers OP 《Journal of biotechnology》2007,127(3):361-372
The spore forming bacterium Clostridium perfringens is a widely occurring pathogen. Vaccines against C. perfringens type B and C are currently manufactured using beta-toxin secreted by virulent C. perfringens strains. Large-scale production of vaccines from virulent strains requires stringent safety conditions and costly detoxification and control steps. Therefore, it would be beneficial to produce this toxin in a safe production host and in an immunogenic, but non-toxic form (toxoid). For high-level expression of beta-toxoid, we cloned the highly active ribosomal rpsF promoter of Bacillus subtilis in a broad host range multicopy plasmid. In B. subtilis, we obtained high intracellular production, up to 200 microg ml(-1) culture. However, the beta-toxoid was poorly secreted. The employed rpsF expression system allowed using the same expression plasmids in other heterologous hosts such as Lactococcus lactis and Streptococcus pneumoniae. In these organisms secretion of beta-toxoid was ten times higher compared to the best producing B. subtilis strain. These results show the usefulness of the rpsF based broad host range expression system. 相似文献
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Gilbert Neuner Benjamin Kreische Dominik Kaplenig Kristina Monitzer Ramona Miller 《Plant, cell & environment》2019,42(7):2065-2074
The frost survival mechanism of vegetative buds of angiosperms was suggested to be extracellular freezing causing dehydration, elevated osmotic potential to prevent freezing. However, extreme dehydration would be needed to avoid freezing at the temperatures down to ?45°C encountered by many trees. Buds of Alnus alnobetula, in common with other frost hardy angiosperms, excrete a lipophilic substance, whose functional role remains unclear. Freezing of buds was studied by infrared thermography, psychrometry, and cryomicroscopy. Buds of A. alnobetula did not survive by extracellular ice tolerance but by deep supercooling, down to ?45°C. An internal ice barrier prevented ice penetration from the frozen stem into the bud. Cryomicroscopy revealed a new freezing mechanism. Until now, supercooled buds lost water towards ice masses that form in the subtending stem and/or bud scales. In A. alnobetula, ice forms harmlessly inside the bud between the supercooled leaves. This would immediately trigger intracellular freezing and kill the supercooled bud in other species. In A. alnobetula, lipophilic substances (triterpenoids and flavonoid aglycones) impregnate the surface of bud leaves. These prevent extrinsic ice nucleation so allowing supercooling. This suggests a means to protect forestry and agricultural crops from extrinsic ice nucleation allowing transient supercooling during night frosts. 相似文献
87.
Julia Wallmeier Diana Bracht Hessa S. Alsaif Gerard W. Dougherty Heike Olbrich Sandra Cindric Mark Dzietko Christoph Heyer Norbert Teig Charlotte Thiels Eissa Faqeih Aqeela Al-Hashim Sameena Khan Ibrahim Mogarri Mohammed Almannai Wadha Al Otaibi Fowzan S. Alkuraya Cordula Koerner-Rettberg Heymut Omran 《American journal of human genetics》2021,108(7):1318-1329
88.
Proteasomes are highly conserved multisubunit protease complexes and occur in the cyto- and nucleoplasm of eukaryotic cells. In dividing cells proteasomes exist as holoenzymes and primarily localize in the nucleus. During quiescence they dissociate into proteolytic core and regulatory complexes and are sequestered into motile cytosolic clusters. Proteasome clusters rapidly clear upon the exit from quiescence, where proteasome core and regulatory complexes reassemble and localize to the nucleus again. The mechanisms underlying proteasome transport and assembly are not yet understood. Here, I summarize our present knowledge about nuclear transport and assembly of proteasomes in yeast and project our studies in this eukaryotic model organism to the mammalian cell system. This article is part of a Special Issue entitled: Ubiquitin–Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf. 相似文献
89.
Nicole Scheuing Reinhard W. Holl Gerd Dockter Julia M. Hermann Sibylle Junge Cordula Koerner-Rettberg Lutz Naehrlich Christina Smaczny Doris Staab Gabriela Thalhammer Silke van Koningsbruggen-Rietschel Manfred Ballmann 《PloS one》2014,9(11)
Background
In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate within-patient variability of oral glucose tolerance.Methods
In total, 4,643 standardized oral glucose tolerance tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 [11.5; 21.5] years, 48.8% females) were studied. Patients included were clinically stable, non-pregnant, and had at least two oral glucose tolerance tests, with no prior lung transplantation or systemic steroid therapy. Transition frequency from any one test to the subsequent test was analyzed and within-patient coefficients of variation were calculated for fasting and two hour blood glucose values. All statistical analysis was implemented with SAS 9.4.Results
A diabetic glucose tolerance was confirmed in 41.2% by the subsequent test. A regression to normal glucose tolerance at the subsequent test was observed in 21.7% and to impaired fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The average within-patient coefficient of variation for fasting blood glucose was 11.1% and for two hour blood glucose 25.3%.Conclusion
In the cystic fibrosis patients studied, a highly variable glucose tolerance was observed. Compared to the general population, variability of two hour blood glucose was 1.5 to 1.8-fold higher. 相似文献90.
HD Nischalke V Schmitz C Luda K Aldenhoff C Berger G Feldmann T Sauerbruch U Spengler J Nattermann 《PloS one》2012,7(8):e42141