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451.
Many disease affect cell behaviour by an effect at the cell surface, often leading to altered communication across the plasma membrane. Two examples of this from our own work are presented. The first concerns the induction of pores, leading to a breach of insulating properties of the cell membrane, by agents as diverse as certain viruses, bacterial and animal toxins, or immune molecules. In each case, membrane damage can be prevented by divalent cations such as Ca2+ or Zn2+. The second example concerns the effect of stress stimuli on the ability of cells to take up glucose. Different stresses, such as hyperthermia, toxic chemicals or infection by certain viruses, cause cells to increase glucose uptake. As with insulin-stimulated glucose uptake, the mechanism is by translocation of the glucose transporter protein from an intracellular (inactive) site to the plasma membrane.  相似文献   
452.
3H-Labelled opiate and enkephalin ligands appear to bind with highest affinity to a single site responsible for their analgesic properties. Administered in vivo, naloxazone, an irreversible opiate, selectively inhibits for over 24 hours the high affinity binding of 3H-labelled mu, and kappa opiates and enkephalins. This inhibition of binding gradually resolves over 3 days, perhaps correlating with receptor turnover. Naloxazone treatment also abolishes morphine, D-ala2-met5-enkephalinamide and betah-endorphin analgesia. Although morphine and D-ala2-met5-enkephalinamide bind with similar potencies to the high affinity site, morphine's potency for the low affinity D-ala2-met5-enkephalinamide site is far less than the enkephalin analog. These results imply that all 3H-ligands examined bind with highest affinity to a mu-like receptor while low affinity D-ala2-met5-enkephalinamide binding, with a KD of 6 nM, represents a delta-like receptor.  相似文献   
453.
Scatchard analyses of [125I]D-ala2-D-leu5-enkephalin binding in rat brain membranes are curvilinear, suggesting low and high affinity sites. Treating the membranes with naloxazone abolishes the high affinity binding with slight effect on low affinity binding. Displacement of [125I]-D-ala2-D-leu5-enkephalin binding by morphine in untreated membranes is biphasic. Displacement by morphine in naloxazone-treated tissue is monophasic, with no inhibition by low concentrations of morphine. Naloxazone treatment has little effect on displacements by unlabeled D-ala2-D-leu5-enkephalin. Binding in N4TG1 neuroblastoma cells, which demonstrates a linear Scatchard plot with single affinity constant similar to that of the low affinity binding in brain, is less sensitive to naloxazone's actions. Naloxazone treatment in vivo inhibits D-ala2-D-leu5-enkephalin analgesia.  相似文献   
454.
  1. Many aquatic organisms can consume parasite larvae, thus hampering parasite transmission; however, information about feeding on them in the presence of an alternative prey remains scarce. When having a food choice, predators may decrease parasite consumption, therefore, it is important to assess the role of parasites in the diet of predators in natural communities with different types of prey available. Our study aims to test whether common freshwater cyclopoids feed on trematode free-living stages (cercariae) when an alternative food source is present.
  2. We experimentally studied ingestion rates of cyclopoids Macrocyclops distinctus fed with cercariae of trematode Diplostomum pseudospathaceum, a common and harmful parasite of freshwater fishes, and ciliates Paramecium caudatum (an alternative prey, known as suitable food for copepods). First, the feeding response of cyclopoids to different densities of each prey was studied. Then, feeding selectivity in the mixtures of cercariae and ciliates was tested.
  3. Feeding rates of cyclopoids increased with prey densities (both ciliates and cercariae) but almost stopped growing at high prey densities, which indicated saturation (Holling type II functional response). In most cases, cyclopoids consumed cercariae at higher rates than ciliates. Maximum ingestion rates estimated from the obtained curves were 37 cercariae ind−1 hr−1 and 17 ciliate ind−1 hr−1.
  4. When exposed to prey mixtures, cyclopoids fed on cercariae selectively. When cercariae were offered to cyclopoids at concentrations exceeding the saturation level, the ingestion of ciliates remained constantly low at all ciliate densities. In contrast, the ingestion of cercariae increased with rising cercariae densities even when ciliates were presented ad libitum, decreasing only at very high prey densities. Possible reasons of such feeding preferences are discussed.
  5. Our study demonstrated that cyclopoids may prefer to feed on cercariae when there is an alternative food choice and can ingest cercariae at high rates. These experimental results could be extended to natural communities, suggesting that cyclopoids can reduce the transmission of parasites and contribute to the incorporation of parasite production in food webs of lentic ecosystems.
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455.
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457.
Methotrexate has been a clinical agent used in cancer, immunosuppression, rheumatoid arthritis, and other highly proliferative diseases for many years, yet its underlying molecular mechanism of action in these therapeutic areas is still unclear. We have previously reported using a chemical proteomics technique on several other potential pharmacodynamic targets of methotrexate. Here, using a frontal affinity chromatography with mass spectrometry detection, we confirm one of these targets, hypoxanthine-guanine amidophosphoribosyltransferase, as a true binder of methotrexate with a Kd of 4.2 μM. These results complement and confirm our recent study, but more importantly, shed light into the mechanism of action of methotrexate in oncology and other highly proliferative diseases and may help explain some unaccounted for effects of this drug. For example, despite the fact that DNA salvage pathway enzymes are highly active, methotrexate can be effective if it only targets enzymes of the de novo pathway.  相似文献   
458.
Mr2034 has been proposed as a kappa opiate. While Mr2034 inhibited the binding of the kappa opiate 3H-ethylketocyclazocine better than unlabeled ethylketocyclazocine, it also displaced the binding of 3H-dihydromorphine and 3H-SKF 10047 more potently than morphine and SKF 10047, respectively. 3H-D-ala2-D-leu5-enkephalin was displaced equally well by Mr2034 and D-ala2-D-leu5-enkephalin. Saturation studies of 3H-Mr2034 binding demonstrated curvilinear Scatchard plots which could be dissected into two components by computer: KD1 0.06 nM, Bmax1 2.49 fmoles/mg tissue; and KD2 2.4 nM, Bmax2 6.57 fmoles/mg tissue. A portion of the higher affinity (KD 0.06 nM) component was inhibited by naloxonazine treatment in vitro (50 nM), suggesting that 3H-Mr2034 bound with very high affinity to mu1 sites. Displacement of 3H-Mr2034 binding by opioids was multiphasic, again implying that 3H-Mr2034 was binding to more than one class, of site. In view of its similar potency in inhibiting mu (3H-dihydromorphine), kappa (3H-ethylketocycla-zocine), sigma (3H-SKF 10047) and delta (3H-D-ala2-D-leu5-enkephalin) opioids Mr2034 might be considered a universal opiate.  相似文献   
459.
Differential genic activity in Paramecium aurelia   总被引:4,自引:0,他引:4  
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460.
The effect of stress (heat shock, arsenite, or Semliki Forest virus [SFV] infection) on the induction of increased hexose transport has been compared with that of insulin. All four treatments increase the Vmax for transport by BHK cells three- to five-fold, with little effect (less than 40% decrease) on Km. Hydrogen peroxide and phenylarsine oxide (PAO) prevent the increase in hexose transport induced by stress treatments as effectively as they do that induced by insulin. Pinocytosis is not affected by any of the four treatments. On the other hand, the induction by insulin is sensitive to amiloride, whereas that by arsenite is not. Rat embryo fibroblasts, which respond poorly to insulin, respond well to arsenite, heat shock, or SFV infection. It is concluded that the stress response is mediated by certain compounds that may be common to those required for the action of insulin, but that those compounds act at a stage subsequent to the function of the insulin receptor.  相似文献   
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