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Stimulation of secretion in exocrine secretory glands leads to the phosphorylation of a 22-kDa membrane protein (protein III) whose function is still unknown [Jahn et al. (1980) Eur. J. Biochem. 112, 345-352; Jahn & S?ling (1980) Proc. Natl Acad. Sci. USA 78, 6903-6906]. This report describes the comparison of this protein with phosphorylated membrane proteins of similar molecular mass in platelets and liver. Incubation of platelets with agents which raise the intracellular cAMP concentration results in the phosphorylation of a 22-kDa protein which is also phosphorylated in membrane preparations by endogenous kinases or by exogenous cAMP-dependent protein kinase. It is shown that this protein is distinct from protein III although both proteins have the same molecular mass and are substrates of cAMP-dependent protein kinase. In contrast to platelets, protein III could be demonstrated in liver microsomes. This indicates that the function of protein III is not exclusively linked to the stimulus-secretion coupling in exocrine cells.  相似文献   
3.
The early effects (0-120 s) of the beta-adrenergic secretagogue isoproterenol (2.10(-5) M) and the muscarinic secretagogue carbamoylcholine (2.10(-6) M) on various parameters of lipid and phospholipid metabolism were studied in isolated guinea pig parotid acinar cells. Both agonists enhanced within 10-20 s the incorporation of radioactive palmitate into the diacylglycerol, the triglyceride, and the phosphatidylinositol fractions but significantly diminished radioactive palmitate recovered in the acyl-CoA fraction. Carbamoylcholine decreased and isoproterenol increased the recovery of radioactive palmitate in the free fatty acid fraction. All changes had returned almost to control levels after 120 s. In cells prelabeled with [3H]arachidonate, carbamoylcholine exerted similar effects, whereas isoproterenol was almost ineffective. Both agonists stimulated the incorporation of radioactive glycerol into diacylglycerols 2-3-fold, while only carbamoylcholine stimulated the incorporation of [32P]phosphate into phosphatidylinositol and phosphatidate. Both agonists induced an increase in total diacylglycerols, carbamoylcholine being about twice as effective as isoproterenol. A lower concentration of carbamoylcholine (6.5.10(-7) M) had the same quantitative effect as 2.10(-5) M isoproterenol on the increase of total diacylglycerols. Even under these conditions carbamoylcholine, but not isoproterenol led to a significant translocation of protein kinase C from the soluble to the particulate fraction. Isoproterenol remained ineffective in this respect also when intracellular free calcium was increased with a calcium ionophore. This is explained by the finding that isoproterenol stimulates preferentially the formation of 2,3-sn-diacylglycerol, and carbamoylcholine preferentially stimulates the formation of 1,2-sn-diacylglycerol. The results indicate that in the guinea pig parotid acinar cell the two agonists do not only lead to activation of a triglyceride lipase (isoproterenol) or phosphoinositide-specific phospholipase(s) (carbamoylcholine), but also to a rapid change of flux through a number of other enzyme-catalyzed reactions involved in diacylglycerol turnover.  相似文献   
4.
Stimulation of secretion in guinea pig exocrine cells is associated with an enhanced synthesis in these cells of 1-O-alkyl-2-sn-acetyl-glycero-3-phosphocholines (PAF) from 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (S?ling, H-D., and Fest, W. (1986) J. Biol. Chem. 261, 13916-13922). This results from a stimulation of the activity of lyso-1-alkylglycerophosphocholine acetyltransferase (EC 2.3.1.67). Here we have analyzed the effects of various agonists on the activity of this enzyme in guinea pig parotid gland microsomes. Carbamoylcholine leads within less than 30 s to a 2- to 4-fold activation of lyso-PAF-acetyltransferase, which persists after solubilization of the microsomal enzyme with octyl glucoside. The calcium ionophore A23187 has a similar though smaller effect. Neither isoproterenol (2 X 10(-5) M), which stimulates exocytosis more than carbachol, nor phorbol ester significantly affected lyso-PAF-acetyltransferase activity. Incubation of microsomes from unstimulated parotid gland acini with cAMP-dependent and calcium/calmodulin-dependent protein kinase resulted in a 4-fold and 2.9-fold activation of lyso-PAF-acetyltransferase activity, respectively. Protein kinase C had no significant effect. Activation with calcium/calmodulin-dependent protein kinase was inhibited by 40 microM trifluoperazine. When microsomes from carbachol-stimulated glands were used, in vitro activation of the enzyme by calcium/calmodulin-dependent protein kinase was almost abolished. Protein phosphatase 2A in vitro strongly reduced lyso-PAF-acetyltransferase activity in microsomes from both stimulated and unstimulated glands, whereas alkaline phosphatase and protein phosphatase 1 had only small effects. Following treatment with protein phosphatase 2A, enzyme activity in microsomes from stimulated glands could be enhanced more than 8-fold by subsequent incubation with calcium/calmodulin-dependent protein kinase. Although unsuccessful attempts have made it impossible so far to demonstrate directly the incorporation of phosphate into lyso-PAF-acetyltransferase, the results reported here strongly suggest that the enzyme in exocrine cells is regulated by phosphorylation-dephosphorylation and that a calcium/calmodulin-dependent protein kinase is responsible for the activation of the enzyme and type-2 protein phosphatases for its inactivation.  相似文献   
5.
Unstable chromosome aberrations induced by in vitro irradiation with zero plus seven low doses of 14.8 MeV D-T neutrons in the range 3.55-244 mGy have been analysed in human peripheral blood lymphocytes. In order to obtain the required large numbers of scored cells for such low doses, fourteen laboratories participated in the experiment. The dose responses for dicentrics, excess acentrics and total aberrations, fitted well to the Y = alpha D model. The alpha coefficient of yield for dicentrics, 1.60 +/- 0.07 X 10(-2) Gy-1, compares well with the values obtained in previous studies with D-T neutrons at somewhat higher doses. Results from a previous collaborative study using 250 kVp X-rays over a comparable dose range indicated the possible existence of a threshold below 50 mGy. In the present study there is no clear evidence for neutrons for such a threshold. However, the data were insufficient to permit the rejection of a possible threshold below approximately 10 mGy.  相似文献   
6.
The subcellular localization and corresponding quaternary state of fluorescent labelled cholera toxin were determined at different time points after exposure to living cells by a novel form of fluorescence confocal microscopy. The compartmentalization and locus of separation of the pentameric B subunits (CTB) from the A subunit (CTA) of the toxin were evaluated on a pixel-by-pixel (voxel-by-voxel) basis by measuring the fluorescence resonance energy transfer (FRET) between CTB labelled with the sulfoindocyanine dye Cy3 and an antibody against CTA labelled with Cy5. The FRET efficiency was determined by a new technique based on the release of quenching of the Cy3 donor after photodestruction of the Cy5 acceptor in a region of interest within the cell. The results demonstrate vesicular transport of the holotoxin from the plasma membrane to the Golgi compartment with subsequent separation of the CTA and CTB subunits. The CTA subunit is redirected to the plasma membrane by retrograde transport via the endoplasmic reticulum whereas the CTB subunit persists in the Golgi compartment.  相似文献   
7.
The effect of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (1), 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine (2) 1-O-hexadecyl-sn-glycero-3-phosphocholine (3), 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (4) and its enantiomer 3-O-octadecyl-2-O-methyl-sn-glycero-1-phosphocholine (5) on the secretion of amylase from guinea pig isolated parotid gland and exocrine pancreatic lobules was examined. Compounds 1, 2 and 4 led to a significant stimulation of amylase release in both systems, effects being already visible between 10-100 pM. Maximal stimulation with compounds 1 and 2 occurred at 5 nM, with compound 4 at 1 nM. Higher concentrations were less effective and at 0.1 microM stimulation was very low. In contrast, compound 5 showed a continuous increase in activity up to 0.01-0.1 microM without a decrease at at higher concentrations. Compound 3 had no effect. For compound 1, its effects on calcium and lipid metabolism have been analyzed and compared with those of the acetylcholine analogue carbamoylcholine. Compound 1 mimicked in every respect the effects of carbamoylcholine. It stimulated the uptake of 45Ca by isolated parotid gland lobules in a non-ionophoretic way. In isolated pancreatic lobules it enhanced the incorporation of [32P]phosphate into phosphatidic acid, phosphatidylinositol and poly(phosphoinositide), increased the formation of diacylglycerols and triacylglycerol, led to the same two-phasic responses of myo-[3H]inositol-labeled polyphosphoinositides, and initiated a rapid short-lasting formation of free inositol triphosphate. Accordingly, 'platelet activating factor(s)' can affect the function of exocrine glands at low concentrations. The effects observed resemble those produced by acetylcholine and result most likely from the interaction of platelet-activating factor with plasma membrane receptors.  相似文献   
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9.
D Perrin  H D S?ling 《FEBS letters》1992,311(3):302-304
Stimulation of secretion in chromaffin and parotid acinar cells is associated with dramatic rearrangements of the subplasmalemmal cytoskeleton, notably of fodrin and F-actin. It has been proposed that a proteolytic cleavage of fodrin resulting from an activation of the neutral calcium activated protease (calpain) could be responsible for these changes. Using an affinity-purified anti-alpha-fodrin antibody, several cleavage products of fodrin could clearly be detected following incubation of total cell homogenates from chromaffin and parotid acinar cells with purified calpain I. On the other hand, maximum stimulation of secretion of chromaffin cells by nicotine, and of parotid acinar cells by carbachol plus isoproterenol, was not associated with an increased appearance of cleavage products of fodrin. This result is not compatible with the 'proteolytic cleavage' hypothesis.  相似文献   
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