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81.
Sodium channel blockers are used clinically to treat a number of neuropathic pain conditions, but more potent and selective agents should improve on the therapeutic index of currently used drugs. In a high-throughput functional assay, a novel sodium channel (Na(V)) blocker, N-[[2'-(aminosulfonyl)biphenyl-4-yl]methyl]-N'-(2,2'-bithien-5-ylmethyl)succinamide (BPBTS), was discovered. BPBTS is 2 orders of magnitude more potent than anticonvulsant and antiarrhythmic sodium channel blockers currently used to treat neuropathic pain. Resembling block by these agents, block of Na(V)1.2, Na(V)1.5, and Na(V)1.7 by BPBTS was found to be voltage- and use-dependent. BPBTS appeared to bind preferentially to open and inactivated states and caused a dose-dependent hyperpolarizing shift in the steady-state availability curves for all sodium channel subtypes tested. The affinity of BPBTS for the resting and inactivated states of Na(V)1.2 was 1.2 and 0.14 microM, respectively. BPBTS blocked Na(V)1.7 and Na(V)1.2 with similar potency, whereas block of Na(V)1.5 was slightly more potent. The slow tetrodotoxin-resistant Na(+) current in small-diameter DRG neurons was also potently blocked by BPBTS. [(3)H]BPBTS bound with high affinity to a single class of sites present in rat brain synaptosomal membranes (K(d) = 6.1 nM), and in membranes derived from HEK cells stably expressing Na(V)1.5 (K(d) = 0.9 nM). BPBTS dose-dependently attenuated nociceptive behavior in the formalin test, a rat model of tonic pain. On the basis of these findings, BPBTS represents a structurally novel and potent sodium channel blocker that may be used as a template for the development of analgesic agents.  相似文献   
82.
Summary A method is described for large scale routine phenotyping of haptoglobin (Hp) which allows complete subtyping without prior purification of the Hp molecule. The procedure includes polyacrylamide gel isoelectric focusing of reduced, neuraminidase treated serum or plasma samples, and nitrocellulose blots developed with the immunoperoxidase technique. Different variables including sample treatment, electrofocusing, blotting procedures, and immunoperoxidase visualization are discussed.Characteristic -chain patterns allow identification of the common allotypes 2FS, 2SS, 2FF, IS, IF, and Johnson. Isoelectric variations in the -chain may also be recognized. For comparison, two-dimensional Hp-patterns are presented. The results from concurrent typing of 600 samples by ordinary starch gel electrophoresis and by the described isofocusing technique, are evaluated.  相似文献   
83.
Summary Corynebacterium glutamicum effectively secretes isoleucine when the precursor 2-ketobutyrate is added to the medium. Isoleucine secretion was studied under different conditions with respect to various parameters, i.e. rate of isoleucine excretion and uptake, concentration gradients of isoleucine, other amino acids and ions, and membrane potential. By comparing these parameters in the presence and absence of the amino acid precursor it has been shown that the efflux of isoleucine in C. glutamicum can neither be explained by a passive diffusion mechanism nor by a process involving functional inversion of the isoleucine uptake carrier. Based on our results concerning the distribution of metabolites and the kinetics of excretion we conclude that isoleucine is excreted in C. glutamicum by a separate, presumably active efflux carrier system.  相似文献   
84.
101 populations of Nordic Draba were investigated for chromosome numbers and crossing relationships. The populations were referred to 16 currently recognized species of Sect. Draba, Sect. Chrysodraba (including the D. alpina complex with D. alpina, D. oxycarpa, and D. corymbosa), and Sect. Drabella. The chromosome data suggest that all populations and species are homoploid. Three species are diploid, and 13 species are polyploids ranging from tetraploid to 16-ploid. Draba alpina is decaploid, D. oxycarpa is octoploid, and D. corymbosa is 16-ploid. The chromosome numbers of D. micropetala (n = 16,4x) and D. adamsii (n = 24,2n = 48, 6x) of Sect. Chrysodraba and D. cinerea (n = 24, 6x) of Sect. Draba were determined for the first time based on Nordic material. The relationships inferred from the crossing data largely agree with those inferred from previously published molecular data, but correspond poorly to relationships inferred from morphology. Inter-populational F1 hybrids in D. fladnizensis were entirely sterile, suggesting that this predominantly inbreeding diploid species comprises at least two sibling species, possibly isolated by genic barriers. Sterile to semifertile F1 hybrids with intermediate chromosome numbers were obtained in 19 interspecific combinations. F2 hybrids were obtained in seven of these combinations. Both Sect. Chrysodraba and the D. alpina complex are probably polyphyletic. The crossing data suggest that the morphologically very similar polyploids D. alpina (10x) and D. oxycarpa (8x) do not have any diploid progenitors in common, and that Sect. Draba forms an intricate allopolyploid complex that also includes D. alpina and D. corymbosa of Sect. Chrysodraba. Draba corymbosa (16x) is probably an intersectional, polyphyletic alloploid derived from D. alpina (10x) and various hexaploids of Sect. Draba. Crossing data also suggest that D. norvegica (6x) is one of the progenitors of the Nordic endemic D. cacuminum (8x). The phenotypic expression of genes encoding taxonomically important indument characters did not follow consistent patterns in interspecific hybrids. This result may explain the discrepancy between genetic and taxonomic relationships in Nordic Draba, and supports the use of wide taxonomic concepts in this highly reticulate genus.  相似文献   
85.
The following taxa of Drimiopsis (Hyacintheceae) are recognized for East Africa (Kenya, Tanzania, Uganda): D. barteri (2n=44), D. botryoides ssp. botryoides (2n=44, 55, 66), D. botryoides ssp. prostrata ssp. nov. (2n = 22), D. maculata and D . sp. A.  相似文献   
86.
Digitonin permeabilization of hepatocytes from control and clofibrate-treated (0.5% by mass, 10 days) male C57bl/6 mice was used to study the intracellular distributions of soluble ('cytosolic') epoxide hydrolase and of catalase. The following conclusions were drawn. (1) About 60% of the total soluble epoxide hydrolase activity in control mouse hepatocytes is situated in the cytosol. (2) The rest is not mitochondrial, but probably peroxisomal. (3) Of the total catalase activity in control mouse hepatocytes, 5-10% is found in the cytosol. (4) Treatment of mice with clofibrate increases the total hepatocyte activity of soluble epoxide hydrolase 4-fold, but does not influence the relative distribution of this enzyme between cytosol and peroxisomes. (5) The total catalase activity is increased 3.5-fold by clofibrate treatment and 15-35% of this activity is shifted from the peroxisomes to the cytosol.  相似文献   
87.
Summary Ontogenetic differentiation of the human thymus was investigated in 50 embryos by means of light and electron microscopic methods in an attempt to clarify the morphogenesis of the complicated microecology of thymic tissue. At the 8th gestational week (g.w.), the primordium of the thymus contains almost exclusively undifferentiated epithelial cells. At the 10th g.w., the epithelial cells in the central part are spindle-shaped. During the subsequent weeks the cortical region of the thymus becomes separated into lobes by mesenchymal septa containing hemopoietic precursor cells and large electronlucent cells with irregularly shaped nuclei. The latter cells are also found in the deeper presumptive medullary regions of the thymus; they differentiate into interdigitating reticulum cells (IDC). The permeation of the medulla of the thymus by non-epithelial IDC occurs concurrently with the formation of cortical and medullary epithelial cells. Between the 12th and 14th g.w. the cortical and medullary differentiation is completed. At this time-stage cortical small lymphocytes differ in morphological shape from medullary lymphocytes, the latter acquiring the appearance of immunocompetent T cells and establishing intimate contact with the IDC.These findings indicate that the thymic cortex and medulla contain different epithelial cells. In addition, the thymic medulla displays cells characterized by the morphology of typical interdigitating reticulum cells of peripheral lymphoid tissue. The structural pattern of the thymus is correlated to morphologically differing lymphoid cell populations in the cortical and medullary regions.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft and by the Sonderforschungsbereich 111The authors dedicate this paper to Professor Helmut Leonhardt on the occasion of his 60th birthday. The authors also appreciate the excellent technical assistance of Mrs. I. Knauer, Mrs. H. Waluk and Mrs. H. Siebke  相似文献   
88.
Summary A major function of the larval salivary glands of Drosophila melanogaster is known to be the production of a mucopolysaccharide that serves as an adhesive during puparium formation. In order to localize the mucosubstances during development substrate histochemical methods were used, and the site of acid phosphatase was demonstrated by the ultrahistochemical lead-salt method. It could be shown that the glue-granules in the corpus cells of larval salivary glands as well as the large secretion vacuoles in the prepupal corpus cells give a positive -amylase-resistent PAS-reaction, which indicates neutral mucosubstances. Granular PAS-positive deposits in the larval and prepupal collum cells were reduced after preincubation with -amylase and may represent glycogen, which has also been seen in electron micrographs of these cells. The Hale-reaction gave a weak indication that acid mucosubstances are present in the larval glue granules and in the large prepupal secretory vacuoles. After digestion of sialic acid with -neuraminidase the weak indication was absent showing that the acid mucosubstances had been sialomucines. Ultrahistochemical demonstration of acid phosphatase indicated the presence of this enzyme in Golgi fields and lysosomal structures. Acid phosphatase seems to be missing in the large secretion vacuoles of the prepupal salivary gland.It is concluded, that the large vacuoles in the corpus cells of prepupal salivary glands represent a secretion product, obviously a mucosubstance. The lysosomal structures, containing acid phosphatase, may be accumulated in preparation for the autolysis of the gland which begins about two hours after the pupal moult, i.e. 15 hours after puparium formation.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft (Ga 97/6).  相似文献   
89.
Pajari  Brita 《Plant and Soil》1995,168(1):563-570
Soil respiration rates under elevated temperature and atmospheric CO2 concentrations were studied in eastern Finland (62° 47N, 30° 58E, 144 m.a.s.1.) around naturally regenerated 20 – 30 years old Scots pine trees, enclosed in open top chambers. The production of CO2 varied spatially and temporally, but clearly followed the changes in temperature measured at the soil surface. However, soil respiration in the open control was higher than that in chambers; i.e. the chamber itself changed the conditions by increasing the temperature, altering the movement of water, and thereby soil moisture. Nevertheless, an elevation in the concentration of atmospheric CO2 raised soil respiration and brought it nearer to the level in the open control. An increase in temperature seemed to inhibit this rise, possibly because of an imbalance between temperature and moisture.  相似文献   
90.
Brita  Nyman 《Physiologia plantarum》1969,22(4):662-670
Nonanal, added in ethannlic solution, in concentrations lower than 40 to 80 μM did not affect the growth of Dipodascus aggregatus, provided the inoculum had been harvested from the exponential phase of growth. Growth could even be inhibited by 80 μM. If the inoculum had been grown to the exponential phase and then for another period, to the acceleration phase, in fresh liquid medium, growth was strongly promoted by 80 μM nonanal. If cells from the exponential phase were grown for another period in the supernatant fluid of centrifuged cultures from the exponential phase, 80 μM affected growth in the following way: in five different experiments growth was not stimulated, in one experiment undoubtedly promoted, and weakly stimulated in another one. The growth of cultures inoculated with cells grown only on malt agar was not affected by 80 μM nonanal. Pretreatment of cells, harvested from the acceleration phase, with nonanal (80 μM) in the presence of ethanol did not diminish the growth-promoting action of nonanal on the cultures inoculated with these cells. Nonanal, in the absence of ethanol, in a concentration of 10 μM did not affect the growth of cells, harvested from the acceleration phase, whereas 100 μM nonanal strongly inhibited growth. An attempt is made to explain the results starting from the endogenous metabolism.  相似文献   
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