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61.
The elderly who reside in single-room occupancy (SRO) hotels often have been depicted as "isolates," lacking the interest or ability to engage primary or secondary support systems. This characterization has not enhanced understanding of how the SRO aged are able to survive in the community. With the use of network analysis techniques, this study demonstrates the inaccuracy of the assertion that these old persons lack significant social support. The data pointed to differences in network size, complexity, intensity, connectedness, and directionality in relation to varying degrees of physical and psychiatric health. 相似文献
62.
The ligand binding properties of presynaptic muscarinic receptors present in purified synaptosomal fraction isolated from the electric organ of Torpedo have been studied, using the specific tritiated antagonist N-methyl-4-piperidylbenzilate ([3H]-4NMPB). Direct and competition binding studies revealed that antagonists bind with high affinity to the presynaptic receptor, with saturability occurring at very low ligand concentration, in a stereospecific manner, and according to a simple mass action law. The kinetic results for [3H]4NMPB binding could best be fitted by a two-step sequential isomerization model.The affinities of both agonists and antagonists decreased as a function of increasing ionic strength. Analysis of agonist binding was performed according to the two-site model suggested by Birdsall and Hulme8. Varying the buffer conditions resulted in changes both in the affinities of the agonist for the two agonist sites and in their relative proportions. For a given buffer composition the proportion of high and low affinity sites is constant, but agonists affinities decrease as a function of increase in ionic strength. The finding that at a given ionic strength the proportion of high and low affinity agonist sites can be manipulated suggests that agonist binding sites in Torpedo receptor may interconvert.The apparent dissociation constants measured in Torpedo physiological buffer for both agonists and antagonists are in the same range as the concentrations affecting synaptosomal ACh release. The affinity of agonists towards the presynaptic muscarinic Torpedo receptor was found to be higher than their affinity towards the postsynaptic muscarinic receptor, e.g. in cat and rabbit irides, mouse cortex, etc., and closely resembles the affinity in mouse medulla pons. The localization of pre- and postsynaptic muscarinic receptors in view of their different binding properties is discussed. 相似文献
63.
64.
The bispyridinium oximes toxogonin [N, N′-oxydimethylene bis (pyridinium 4-aldoxim) dichloride] and its structural analogs HS-3, HS-6, HI-6 and MMB-4, and the bispyridinium salt SAD-128, which serve as antidotes to certain types of organophosphorus poisoning, bind competitively to mouse brain muscarinic receptors. This was determined in vitro employing the potent and specific muscarinic antagonist 3H-4NMPB (3H-4-N-methyl piperidyl benzilate). All the bispyridinium compounds also exerted a mild anti-acetylcholine activity (Kd = 10?4?10?5M) measured physiologically in the guinea pig ileum, which correlated well with the dissociation constants obtained from binding studies with mouse brain homogenate. The most potent muscarinic blocker was SAD-128 (K′d = (7.1 ± 1.2) × 10?6M for whole mouse brain), whose remarkable therapeutic action against soman intoxication may be partly attributed to this antimuscarinic activity.The binding data are best fitted by a competitive model, and the deviation from the law of mass action observed here may be related either to the heterogeneity of muscarinic receptors in the mouse brain or to nonequivalency of the number of binding sites for bisquaternary pyridines and 4-NMPB. 相似文献
65.
A possible contribution of metabolic processes to the tolerance to cyclohexamine (l-(l-phenylcyclohexyl) ethylamine) was investigated by determining the kinetics of brain and liver uptake of the labeled drug. A similar time course was found for both naive and tolerant mice. In addition, the amount of the drug uptaken by the brain was found to be linearly dependent on the dose injected in both groups. The possibility of adaptive changes in brain enzymes was investigated using mouse brain acetylcholinesterase (AcChE, E.C.3.1.1.7) as a model of a putative enzyme, affected by phencyclidine derivatives. Although brain AcChE is believed to be chronically affected by these drugs in vivo, no measurable changes could be observed in the amount, the affinity towards diverse ligands or the kinetic properties of this enzyme, between naive, cyclohexamine-tolerant and physostigmine tolerant mice. Possible changes in receptors as the mechanism of tolerance induction were tested by determining the amount of the central muscarinic receptor and its affinity towards a highly specific antimuscarinic ligand in vitro. When comparing naive animals to mice tolerant to cyclohexamine, physostigmine and oxotremorine, no measurable differences could be found in any of these parameters. Repeated injections of cyclohexamine together with scopolamine prevented tolerance development to the former. The possibility of homeostatic events as tolerance mechanism is presented and discussed. 相似文献
66.
Tolerance to physostigmine salicylate was induced in mice using various schedules of s.c. injections. The rate and degree of tolerance development were assessed by comparing the ED50 values (equipotent doses) and by comparing the peak effects induced by a constant dose. These were measured on four systemic responses induced by the drug — hypothermia, tremor, salivation, and the effects measured in the rotarod test. The degree of tolerance development was found to be dose-dependent with a maximal achievable tolerance for every dose. The tolerance development to the four systemic effects differed in time course: tolerance to the hypothermia was induced even with daily injections, while tolerance to the salivation and rotarod effects could be detected only when the drug was given every 4 h. No tolerance developed to the tremor with any of the schedules and doses used. The maximal achievable tolerance degree and the pattern of changes of the duration were different for each systemic effect. The tolerance was found to be reversible, with different rates of recovery, for the different effects. The tolerance state could not be correlated with changes in the pattern of brain acetylcholinesterase (AcChE) inhibition by physostigmine in vivo or with changes in the rate of the enzyme's spontaneous reactivation.Scopolamine. HBr given 10 min before physostigmine prevented tolerance development. In addition, cross-tolerance to various muscarinic agonists and cholinesterase inhibitors was found in the physostigmine-tolerant mice. The correlation between these results and our previous findings concerning possible biochemical adaptations is presented and discussed. 相似文献
67.
A symmetrical cross-tolerance was found between two phencyclidine derivatives-phencyclidine and cyclohexamine-and also between two cholinergic drugs-physostigmine and oxotremorine. On the other hand, mice rendered tolerant to the phencyclidine derivatives showed cross-tolerance to these cholinergic drugs, but no cross-tolerance was observed in the opposite direction.The applicability of such experiments to the elucidation of neurochemical interactions of centrally acting drugs is discussed. 相似文献
68.
S Cherkez H Yellin Y Kashman B Yaavetz M Sokolovsky 《Journal of medicinal chemistry》1979,22(1):18-21
The synthesis of a new series of N,N'-disubstituted 6,7-diazabicyclo[3.2.2]nonane derivatives is described. The antimuscarinic potency of these drugs was evaluated in the guinea pig ileum and compared to that of atropine sulfate. All the drugs tested competitively inhibited the acetylcholine-induced contractions. Kd values were calculated and, in several cases, compared to those obtained by direct binding to the muscarinic receptor from mouse brain. The order of potencies followed that which is known for various tropine and pseudotropine esters; that is, the 3alpha configuration is more potent than the 3beta configuration, and the quaternary analogues are more potent than the tertiary ones. The antimuscarinic activity of the drugs is dicussed in terms of their acetylcholine-like molecular arrangement that gives rise to a characteristic interaction pharmacophore. 相似文献
69.
70.
Kesler G Masychev V Sokolovsky A Alexandrov M Kesler A Koren R 《Journal of clinical laser medicine & surgery》2003,21(4):209-217
OBJECTIVE: The objective of this study was to evaluate a new optical method - photon undulatory non-linear conversion (PNC)--for use in different stages of caries detection. BACKGROUND DATA: Caries should be considered an infectious disease managed by risk assessment, early detection, and preventive therapies, rather than simply "drilling and filling." MATERIAL AND METHODS: Fluorescence emission spectroscopy was performed in vitro on 90 extracted teeth, with intact occlusal surfaces. This system differs from the basic Diagnodent unit in its ability to distinguish between different tissue components with respect to their spectrums. Histological analysis served as the gold standard for verification. The teeth sections correspond to the specific point with the highest reading of the detector. The system was compared to visual inspection, probing, and x-ray methods. The system tested (helium-neon [He-Ne], lambda = 633 nm) has a fiber optic device that delivers radiation to the tooth and a spectrophotometer device that detects bacterial porphyrins fluorescence, allowing detection of caries, fillings, and calculus by simultaneous measurement of backscattering and fluorescence intensity. RESULTS: The system tested provides quantitatively reproducible measurements and detection even through sound enamel of more than 1 mm in thickness. CONCLUSION: The PNC method detects different stages of caries lesions in real time, and it exceeds x-rays in sensitivity, without any ionizing radiation. Preliminary results showed a high potential of using the PNC method in clinical practice (98% accuracy) in comparison to the other methods. 相似文献