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排序方式: 共有106条查询结果,搜索用时 562 毫秒
81.
Xie J Poda GI Hu Y Chen NX Heier RF Wolfson SG Reding MT Lennon PJ Kurumbail RG Selness SR Li X Kishore NN Sommers CD Christine L Bonar SL Venkatraman N Mathialagan S Brustkern SJ Huang HC 《Bioorganic & medicinal chemistry》2011,19(3):1242-1255
Installation of sites for metabolism in the lead compound PHA-767408 was the key focus of the IKK-2 inhaled program. This paper reports our efforts to identify a novel series of aminopyridinecarboxamide-based IKK-2 inhibitors, which display low nanomolar potency against IKK-2 with long duration of action (DOA), and metabolically labile to phase I and/or phase II metabolizing enzymes with potential capability for multiple routes of clearance. Several compounds have demonstrated their potential usefulness in the treatment of asthma and chronic obstructive pulmonary disease (COPD). 相似文献
82.
Outbreaks of plague (Yersinia pestis) among great gerbils (Rhombomys opimus) generally require a high host abundance to be initiated. The duration of an outbreak is expected to depend on the subsequent development of this abundance; however, prediction is nontrivial due to the complexity of the gerbil–plague system. The aim of this study was to investigate how the duration of outbreaks depends on different types of host population dynamics generated from: a cyclic model; an autoregressive model giving irregular fluctuations; and a simple model with uncorrelated fluctuations. For each model, outbreak duration was studied under various levels of mean and variability of host abundance. Its focus on the effect of different gerbil dynamics sets this study apart from the few published studies on diseases in dynamic host populations. Plague outbreaks were simulated in a cellular automaton model based on statistical analysis of archived records of plague and host abundance. Temporal autocorrelation was found to make outbreak duration less sensitive to changes in mean abundance than uncorrelated fluctuations. Cyclicity had little effect on the mean duration of outbreaks, but resulted in a multimodal distribution. For all three types of gerbil dynamics, increased variability in gerbil abundance reduced the duration of outbreaks when the mean abundance was high (paralleling results on the risk of species extinction in fluctuating environments), but increased their duration when the mean abundance was lower. Spatial heterogeneity was briefly tested and produced longer outbreaks than the homogenous case. The results are relevant to predicting plague activity in populations of great gerbils. 相似文献
83.
Christoph Heier Franz P. W. Radner Tarek Moustafa Renate Schreiber Susanne Grond Thomas O. Eichmann Martina Schweiger Albrecht Schmidt Ines K. Cerk Monika Oberer H.-Christian Theussl Jacek Wojciechowski Josef M. Penninger Robert Zimmermann Rudolf Zechner 《The Journal of biological chemistry》2015,290(43):26141-26150
The anabolism and catabolism of myocardial triacylglycerol (TAG) stores are important processes for normal cardiac function. TAG synthesis detoxifies and stockpiles fatty acids to prevent lipotoxicity, whereas TAG hydrolysis (lipolysis) remobilizes fatty acids from endogenous storage pools as energy substrates, signaling molecules, or precursors for complex lipids. This study focused on the role of G0/G1 switch 2 (G0S2) protein, which was previously shown to inhibit the principal TAG hydrolase adipose triglyceride lipase (ATGL), in the regulation of cardiac lipolysis. Using wild-type and mutant mice, we show the following: (i) G0S2 is expressed in the heart and regulated by the nutritional status with highest expression levels after re-feeding. (ii) Cardiac-specific overexpression of G0S2 inhibits cardiac lipolysis by direct protein-protein interaction with ATGL. This leads to severe cardiac steatosis. The steatotic hearts caused by G0S2 overexpression are less prone to fibrotic remodeling or cardiac dysfunction than hearts with a lipolytic defect due to ATGL deficiency. (iii) Conversely to the phenotype of transgenic mice, G0S2 deficiency results in a de-repression of cardiac lipolysis and decreased cardiac TAG content. We conclude that G0S2 acts as a potent ATGL inhibitor in the heart modulating cardiac substrate utilization by regulating cardiac lipolysis. 相似文献
84.
W Ryan Easterday Kyrre L Kausrud Bastiaan Star Lise Heier Bradd J Haley Vladimir Ageyev Rita R Colwell Nils Chr Stenseth 《The ISME journal》2012,6(2):231-236
Plague, caused by the bacterium Yersinia pestis, is a mammalian vector-borne disease, transmitted by fleas that serve as the vector between rodent hosts. For many pathogens, including Y. pestis, there are strong evolutionary pressures that lead to a reduction in ‘useless genes'', with only those retained that reflect function in the specific environment inhabited by the pathogen. Genetic traits critical for survival and transmission between two environments, the rodent and the flea, are conserved in epizootic/epidemic plague strains. However, there are genes that remain conserved for which no function in the flea–rodent cycle has yet been observed, indicating an additional environment may exist in the transmission cycle of plague. Here, we present evidence for highly conserved genes that suggests a role in the persistence of Y. pestis after death of its host. Furthermore, maintenance of these genes points to Y. pestis traversing a post-mortem path between, and possibly within, epizootic periods and offering insight into mechanisms that may allow Y. pestis an alternative route of transmission in the natural environment. 相似文献
85.
DOMINIK LERMEN BRUNHILDE BLÖMEKE ROBERT BROWNE ANN CLARKE PAUL W. DYCE THOMAS FIXEMER GÜNTER R. FUHR WILLIAM V. HOLT KATARINA JEWGENOW RHIANNON E. LLOYD STEFAN LÖTTERS MARTIN PAULUS GORDON MCGREGOR REID DANIEL H. RAPOPORT DAVID RAWSON JENNIFER RINGLEB OLIVER A. RYDER GABRIELE SPÖRL THOMAS SCHMITT MICHAEL VEITH PAUL MÜLLER 《Molecular ecology》2009,18(6):1030-1033
Cryobanking, the freezing of biological specimens to maintain their integrity for a variety of anticipated and unanticipated uses, offers unique opportunities to advance the basic knowledge of biological systems and their evolution. Notably, cryobanking provides a crucial opportunity to support conservation efforts for endangered species. Historically, cryobanking has been developed mostly in response to human economic and medical needs — these needs must now be extended to biodiversity conservation. Reproduction technologies utilizing cryobanked gametes, embryos and somatic cells are already vital components of endangered species recovery efforts. Advances in modern biological research (e.g. stem cell research, genomics and proteomics) are already drawing heavily on cryobanked specimens, and future needs are anticipated to be immense. The challenges of developing and applying cryobanking for a broader diversity of species were addressed at an international conference held at Trier University (Germany) in June 2008. However, the magnitude of the potential benefits of cryobanking stood in stark contrast to the lack of substantial resources available for this area of strategic interest for biological science — and society at large. The meeting at Trier established a foundation for a strong global incentive to cryobank threatened species. The establishment of an Amphibian Ark cryobanking programme offers the first opportunity for global cooperation to achieve the cryobanking of the threatened species from an entire vertebrate class. 相似文献
86.
87.
Marker assisted selection using best linear unbiased prediction 总被引:1,自引:0,他引:1
88.
89.
Both the Entamoeba histolytica lectin, a virulence factor for the causative
agent of amebiasis, and the mammalian hepatic lectin bind to
N-acetylgalactosamine (GalNAc) and galactose (Gal) nonreducing termini on
oligosaccharides, with preference for GalNAc. Polyvalent GalNAc-
derivatized neoglycoproteins have >1000-fold enhanced binding affinity
for both lectins (Adler,P., Wood,S.J., Lee,Y.C., Lee,R.T., Petri,W.A.,Jr.
and Schnaar,R.L.,1995, J. Biol. Chem ., 270, 5164-5171). Substructural
specificity studies revealed that the 3-OH and 4-OH groups of GalNAc were
required for binding to both lectins, whereas only the E.histolytica lectin
required the 6-OH group. Whereas GalNAc binds with 4-fold lower affinity to
the E.histolytica lectin than to the mammalian hepatic lectin,
galactosamine and N-benzoyl galactosamine bind with higher affinity to the
E. histolytica lectin. Therefore, a synthetic scheme for converting
polyamine carriers to poly-N-acyl galactosamine derivatives (linked through
the galactosamine primary amino group) was developed to test whether such
ligands would bind the E.histolytica lectin with high specificity and high
affinity. Contrary to expectations, polyvalent derivatives including
GalN6lys5, GalN4desmosine, GalN4StarburstTMdendrimer, and
GalN8StarburstTMdendrimer demonstrated highly enhanced binding to the
mammalian hepatic lectin but little or no enhancement of binding to the
E.histolytica lectin. We propose that the mammalian hepatic lectin binds
with greatest affinity to GalNAc "miniclusters," which mimic branched
termini of N-linked oligosaccharides, whereas the E.histolytica lectin
binds most effectively to "maxiclusters," which may mimic more widely
spaced GalNAc residues on intestinal mucins.
相似文献
90.
Potential Uptake of Escherichia coli O157:H7 from Organic Manure into Crisphead Lettuce 总被引:3,自引:0,他引:3
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Gro S. Johannessen Gunnar B. Bengtsson Berit T. Heier Sylvia Bredholt Yngvild Wasteson Liv Marit R?rvik 《Applied microbiology》2005,71(5):2221-2225
To investigate the potential transfer of Escherichia coli O157:H7 from contaminated manure to fresh produce, lettuce seedlings were transplanted into soil fertilized with bovine manure which had been inoculated with approximately 104 CFU g−1 E. coli O157:H7. The lettuce was grown for approximately 50 days in beds in climate-controlled rooms in a greenhouse. As the bacterium was not detected in the edible parts of the lettuce, the outer leaves of the lettuce, or the lettuce roots at harvest it was concluded that transmission of E. coli O157:H7 from contaminated soil to lettuce did not occur. The pathogen persisted in the soil for at least 8 weeks after fertilizing but was not detected after 12 weeks. Indigenous E. coli was detected only sporadically on the lettuce at harvest, and enterococci were not detected at all. The numbers of enterococci declined more rapidly than those of E. coli in the soil. Pseudomonas fluorescens, which inhibited growth of E. coli O157:H7 in vitro, was isolated from the rhizosphere. 相似文献