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91.
Goal, Scope and Background The paper describes different ecotoxicity effect indicator methods/approaches. The approaches cover three main groups, viz.
PNEC approaches, PAF approaches and damage approaches. Ecotoxicity effect indicators used in life cycle impact assessment
(LCIA) are typically modelled to the level of impact, indicating the potential impact on 'ecosystem health'. The few existing
indicators, which are modelled all the way to damage, are poorly developed, and even though relevant alternatives from risk
assessment exist (e.g. recovery time and mean extinction time), these are unfortunately at a very early stage of development,
and only few attempts have been made to include them in LCIA.
Methods The approaches are described and evaluated against a set of assessment criteria comprising compatibility with the methodological
requirements of LCIA, environmental relevance, reproducibility, data demand, data availability, quantification of uncertainty,
transparency and spatial differentiation.
Results and Discussion The results of the evaluation of the two impact approaches (i.e. PNEC and PAF) show both pros and cons for each of them.
The assessment factor-based PNEC approaches have a low data demand and use only the lowest data (e.g. lowest NOEC value).
Because it is developed in tiered risk assessment, and hence makes use of conservative assessment factors, it is not optimal,
in its present form, to use in the comparative framework of LCIA, where best estimates are sought. The PAF approaches have
a higher data demand but use all data and can be based on effect data (PNEC is no-effect-based), thus making these approaches
non-conservative and more suitable for LCIA. However, indiscriminate use of ecotoxicity data tends to make the PAF-approaches
no more environmentally relevant than the assessment factor-based PNEC approaches. The PAF approaches, however, can at least
in theory be linked to damage modelling. All the approaches for damage modelling which are included here have a high environmental
relevance but very low data availability, apart from the 'media recovery-approach', which depends directly on the fate model.
They are all at a very early stage of development.
Conclusion Recommendations and Outlook. An analysis of the different PAF approaches shows that the crucial point is according to which
principles and based on which data the hazardous concentration to 50% of the included species (i.e. HC50) is estimated. The
ability to calculate many characterisation factors for ecotoxicity is important for this impact category to be included in
LCIA in a proper way. However, the access to effect data for the relevant chemicals is typically limited. So, besides the
coupling to damage modelling, the main challenge within the further development and improvement of ecotoxicity effect indicators
is to find an optimal method to estimate HC50 based on little data. 相似文献
92.
Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis of a variety of angiogenic factors, via the nuclear factor (NF)-kappaB activation. Recently, we reported that PAF upregulates MMP-9 expression in a NF-kappaB-dependent manner. In this study, we investigated the signaling pathway involved in PAF-induced MMP-9 expression in ECV304 cells. Our current data indicate that the Ca(2+)- or phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is necessary for PAF-induced MMP-9 expression. Furthermore, PAF-induced NF-kappaB activation was blocked by selective inhibitors of Ca(2+), PI3K, or extracellular signal-regulated kinase (ERK). Our results suggest that PAF-induced MMP-9 expression, in a NF-kappaB-dependent manner, is regulated by Ca(2+), PI3K and ERK signaling pathways. 相似文献
93.
PAF is involved in the Mycoplasma arthritidis superantigen-triggering pathway for iNOS and COX-2 expression in murine peritoneal cells 总被引:1,自引:0,他引:1
We investigated the capacity of Mycoplasma arthritidis mitogen (MAM) to induce (a) expression of the inducible enzymes cyclo-oxygenase (COX-2) and nitric oxide synthase (iNOS), (b) production of prostaglandin E2 (PGE2) and nitric oxide (NO), and (c) involvement of platelet-activating factor (PAF) in the MAM-induced activation pathway. Resident peritoneal cells from C3H/HePas mice were incubated with MAM in the presence or absence of a PAF-antagonist (WEB2170) or COX-2 inhibitors (nimesulide or NS398). Enzyme expression was evaluated by immunoblotting, PGE2 by EIA, and NO by Griess reaction. Following MAM-stimulation of peritoneal cells, expression of COX-2 was detected at 3 h (peak levels at 12 h) and of iNOS at 6 h (peak levels at 20 h). PGE2 increased till 20 h, decreasing thereafter, whereas NO increased with time. WEB2170 (5 x 10(-5) M) treatment caused 44% inhibition of NO output and reduced iNOS expression (48% at the peak of expression). Concomitant treatment with WEB2170 and nimesulide (10(-5) M) reversed these inhibitory effects. WEB2170 reduced COX-2 expression (43% at the peak of expression) and prevented the decline in PGE2 levels after 20 h. These results suggest the involvement of PAF in the signaling pathway triggered by MAM that leads to expression of iNOS and COX-2, and show that PAF regulates the production of NO, possibly by controlling levels of PGE2. 相似文献
94.
95.
Francescangeli E. Lang D. Dreyfus H. Boila A. Freysz L. Goracci G. 《Neurochemical research》1997,22(10):1299-1307
Platelet-Activating Factor (PAF) is a potent lipid mediator involved in physiological and pathological events in the nervous tissue where it can be synthesized by two distinct pathways. The last reaction of the de novo pathway utilizes CDPcholine and alkylacetylglycerol and is catalyzed by a specific phosphocholinetransferase (PAF-PCT) whereas the remodelling pathway ends with the reaction catalyzed by lyso-PAF acetyltransferase (lyso-PAF AcT) utilizing lyso-PAF, a product of phospholipase A2 activity, and acetyl-CoA. The levels of PAF in the nervous tissue are also regulated by PAF acetylhydrolase that inactivates this mediator. We have studied the activities of these enzymes during cell proliferation and differentiation in two experimental models: 1) neuronal and glial primary cell cultures from chick embryo and 2) LA-N-1 neuroblastoma cells induced to differentiate by retinoic acid (RA). In undifferentiated neuronal cells from 8-days chick embryos the activity of PAF-PCT was much higher than that of lyso-PAF AcT but it decreased during the period of cellular proliferation up to the arrest of mitosis (day 1–3). During this period no significant changes of lyso-PAF AcT activity was observed. Both enzyme activities increased during the period of neuronal maturation and the formation of cellular contacts and synaptic-like junctions. The activity of PAF acetylhydrolase was unchanged during the development of the neuronal cultures. PAF-PCT activity did not change during the development of chick embryo glial cultures but lyso-PAF AcT activity increased up to the 12th day. RA treatment of LA-N-1 cell culture in proliferation decreased PAF-PCT activity and had no significant effect on lyso-PAF AcT and PAF acetylhydrolase indicating that the synthesis of PAF by the enzyme catalyzing the last step of the de novo pathway is inhibited when the LA-N-1 cells are induced to differentiate. These data suggest that: 1) in chick embryo primary cultures, both pathways are potentially able to contribute to PAF synthesis during development of neuronal cells particularly when they form synaptic-like junctions whereas, during development of glial cells, only the remodelling pathway might be particularly active on synthesizing PAF; 2) in LA-N-1 neuroblastoma cells PAF-synthesizing enzymes coexist and, when cells start to differentiate the contribution of the de novo pathway to PAF biosynthesis might be reduced. 相似文献
96.
ANGELA H. C. S. LOPES PATRICIA M. L. DUTRA CLAUDIA O. RODRIGUES MAURILIO J. SOARES JAYME ANGLUSTER RENATO S. B. CORDEIRO 《The Journal of eukaryotic microbiology》1997,44(4):321-325
ABSTRACT. The effects of platelet-activating factor (PAF), at doses ranging from 10−6 M to 10−10 M, on cell growth and on cell differentiation of Herpetomonas muscarum muscarum were investigated. Cell differentiation was evaluated by both light and electron microscopy. At the concentrations used, PAF did not interfere with the protozoan growth. However, parasites grown in the presence of PAF (10−6 M) were significantly more differentiated than those grown in the absence of PAF, since the first day of culture. On the first two days of culture, PAF doses ranging from 10−10 M to 10−7 M, did not significantly interfere with the differentiation of these parasites, although after the third day of culture, all PAF doses used significantly increased the protozoan differentiation. Specific PAF receptor antagonists totally abrogated (WEB 2086 and WEB 2170)or significantly decreased (BN 52021) PAF effect on cell differentiation. These findings indicate PAF triggers the process of cell differentiation in Herpetomonas muscarum muscarum and suggest these parasites have receptors for PAF. 相似文献
97.
PAF受体及其信号传导 总被引:2,自引:0,他引:2
吕小燕 《生物化学与生物物理进展》1994,21(3):211-214
血小板激活因子是一种强力的磷脂介质,普遍认为它经其特异受体而起作用.最近已克隆出PAF膜受体的cDNA.文章综述了有关PAF受体及其信号传导研究的新进展. 相似文献
98.
Ayana Hasegawa Miwa Watanabe Hironari Osada Misato Ogawa Hikaru Ohno Nanako Yanuma Kazuaki Sasaki Minoru Shimoda Junsuke Shirai Keitaro Ohmori 《Biochemical and biophysical research communications》2018,495(3):2184-2188
A time-of-day-dependent variation in IgE-mediated passive systemic anaphylaxis was previously reported in ICR mice. In the present study, we investigated time-of-day-dependent variations in IgE-, histamine-, and platelet-activating factor (PAF)-mediated systemic anaphylaxis in C57BL/6, BALB/c, and NC/Nga mice at 9:00?h and 21:00?h, and evaluated the potential influence of glucocorticoids (GCs) on these variations. We found significant time-of-day-dependent variations in IgE-mediated systemic anaphylaxis in C57BL/6 mice, and in histamine- and PAF-mediated systemic anaphylaxis in BALB/c mice. Significant daily variations in IgE-, histamine-, and PAF-mediated systemic anaphylaxis were not observed in NC/Nga mice. Pretreatment with dexamethasone and adrenalectomy abolished the daily variations in IgE-mediated systemic anaphylaxis in C57BL/6 mice and in PAF-mediated systemic anaphylaxis in BALB/c mice, suggesting that GCs from adrenal glands are pivotal in regulating these variations. In contrast, pretreatment with dexamethasone and adrenalectomy did not abolish the daily variation in histamine-mediated systemic anaphylaxis in BALB/c mice, suggesting that GC-independent and adrenal gland-independent mechanisms are important for the variation. The present study demonstrated that time-of-day-dependent variations in systemic anaphylaxis differed among inbred mouse strains and with anaphylaxis-inducing substances. Thus, mouse strains, time of experiment, and anaphylaxis-inducing substances used must be considered to obtain appropriate experimental results. 相似文献
99.
C Kadiri J Masliah M Bachelet B B Vargaftig G Béréziat 《Journal of cellular biochemistry》1989,40(2):157-164
The stimulation of cultured guinea pig alveolar macrophages by the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, or by the phospholipid inflammatory mediator platelet activating factor (PAF) induced an increase in arachidonic acid release and its cyclooxygenase products. This release, which was mimicked by the association of threshold concentrations of the calcium ionophore A 23187 and of the protein kinase C activator tetradecanoyl phorbol acetate arose mainly from diacyl- and alkyl-acyl-phosphatidylcholine and phosphatidylinositol. Using [1-14C]arachidonic acid-labeled membranes as an endogenous substrate as well as dioleoyl-phosphatidyl [14C]ethanolamine as an exogenous substrate, we showed that phospholipase A2 activity of stimulated macrophages increases upon stimulation. Treatment of macrophages by prostaglandin E2 decreased the arachidonic acid release elicited by the chemotactic peptide and PAF. Furthermore, prostaglandin E2 increased and PAF decreased the cellular content in cyclic AMP. From these results we suggest that an initial stimulation of alveolar macrophages by a bacterial signal initiates the sequential activation of a phospholipase C and of phospholipase A2, leading to the release of PAF and eicosanoids. These mediators may in turn modulate the cell response by increasing or decreasing cyclic AMP, Ca2+, or diacyglycerol macrophage content. 相似文献
100.
Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) (PAF) is a potent signaling phospholipid which has pleiotropic biological properties in addition to platelet activation. PAF has been detected in the spermatozoa in a number of species. The concentration of PAF is inversely related to human spermatozoal quality. There are no reports on the presence of PAF in nonhuman primate spermatozoa. Therefore, the primary objective of this study was to determine if PAF is present in the spermatozoa from the squirrel monkey (which is a seasonal breeder). A second objective was to determine if PAF levels change from the breeding to the nonbreeding season. Endogenous lipids were extracted from mature Bolivian squirrel monkeys (Saimiri boliviensis) spermatozoa and assayed for the presence of PAF by [125I] radioimmunoassay. PAF was detected in all samples assayed. PAF levels were significantly higher (P< 0.01) during the breeding season (mean: 3.58 ng/106 spermatozoa) than the nonbreeding season (mean: 0.76 ng/106 spermatozoa). The data demonstrate that PAF is present in squirrel monkey spermatozoa, with higher levels found during the breeding season. Additional studies are warranted to elucidate the role of PAF in spermatozoa function. Am. J. Primatol. 45:301–305, 1998. © 1998 Wiley-Liss, Inc. 相似文献