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71.
The contribution of proton spectroscopic (PS) imaging to magnetic resonance (MR) imaging of the liver was assessed at 0.5 T in 55 patients with known or suspected hepatic malignancy. PS images were compared subjectively with T1- and T2-weighted spin-echo (SE) images for hepatic lesion detection and conspicuity. For hepatic metastases (n = 27), PS images were equal to T1-weighted images in lesion detection in 17 patients but showed fewer lesions in five patients and false-negative results in two. When compared with T2-weighted images, PS images depicted more lesions in six patients, an equal number of lesions in 18, and fewer lesions in two. Hepatomas (n = 8) were detected with each sequence in all patients. Hepatomas were often more conspicuous on PS images than on T2-weighted images; they were of equal conspicuity on PS and T1-weighted images in most cases. Whereas fatty infiltration (n = 16) appeared on PS images as areas of low signal intensity similar to that of paraspinal muscle, it produced no detectable abnormality on either T1- or T2-weighted images. PS imaging is inferior to T1-weighted SE imaging in the detection of hepatic metastases. The major role of PS imaging at intermediate field strength is to differentiate focal fatty infiltration from hepatic metastases. 相似文献
72.
The treatment of the patient with chronic obstructive pulmonary disease (COPD) described here is one in which psychosocial assets are increased, the effect of life change is minimized, and the emotional defenses are utilized to cope with the disease process. Problems in the patient's environment are surmounted when the patient maintains a therapy program that allows him or her to meet the requirements of daily living. 相似文献
73.
Malignant strictures of the afferent jejunal limbs are difficult to treat. Surgical revision and chronic external drainage, two commonly used palliative procedures, have significant associated morbidity. A combined transhepatic and peroral approach was used to stent malignant jejunal strictures in two patients, allowing antegrade internal drainage of biliary and pancreatic secretions. Excellent palliation was achieved, and there were no associated complications. 相似文献
74.
Rationale and Objectives Conflict procedures are used to study mechanisms underlying the anxiolytic effects of benzodiazepines (BZs). We established
a conflict procedure with rhesus monkeys in order to examine the role of GABAA receptors in the anxiolytic-like effects of BZs.
Methods Four rhesus monkeys responded under a two-component multiple schedule in which responding was maintained under a fixed-ratio
schedule of food delivery in the absence (non-suppressed responding) and presence (suppressed responding) of response-contingent
electric shock.
Results Conventional BZs (alprazolam, flunitrazepam, clonazepam, nitrazepam, lorazepam, bromazepam, diazepam, flurazepam, clorazepate,
chlordiazepoxide) engendered increases in the average rates of suppressed responding at low to intermediate doses and decreased
the average rates of non-suppressed responding at higher doses. Positive correlations were observed when the therapeutic potencies
of BZs in humans were compared with potencies to increase the rates of suppressed responding (R
2=0.83) or decrease the rates of non-suppressed responding (R
2=0.60). The 5-HT1A agonist buspirone increased the rates of suppressed responding, although the effects were modest, whereas the opioid morphine
lacked anti-conflict effects. The BZ antagonist flumazenil also modestly increased the rates of suppressed responding. A relatively
low dose of flumazenil enhanced, while a high dose blocked, alprazolam’s anti-conflict effects. Compounds selective for α1 subunit-containing GABAA receptors (zolpidem, zaleplon, CL218,872) engendered relatively weak increases in the rates of suppressed responding.
Conclusions A rhesus monkey conflict procedure was established with predictive validity for therapeutic doses in people and provided evidence
that anxiolytic-like effects of BZs can occur with relatively low intrinsic efficacy at GABAA receptors and are reduced by α1GABAA receptor selectivity.
This research was supported by U.S.P.H.S. grants DA11792 and RR00168 相似文献
75.
Two cases of intracerebral pneumatocele following trauma are presented. One to two months after initial treatment both patients had deteriorating neurologic status. The diagnosis was made by radiography. When a pneumatocele is suspected clinically, computed tomography can play a vital role in determining the precise location of the gas collection, its relationship to the fracture site, and the amount of mass effect on the brain. 相似文献
76.
77.
RJ Mann NE Nasr JK Sinfield E Paci D Donnelly 《British journal of pharmacology》2010,160(8):1973-1984
BACKGROUND AND PURPOSE
Exendin-4 (exenatide, Ex4) is a high-affinity peptide agonist at the glucagon-like peptide-1 receptor (GLP-1R), which has been approved as a treatment for type 2 diabetes. Part of the drug/hormone binding site was described in the crystal structures of both GLP-1 and Ex4 bound to the isolated N-terminal domain (NTD) of GLP-1R. However, these structures do not account for the large difference in affinity between GLP-1 and Ex4 at this isolated domain, or for the published role of the C-terminal extension of Ex4. Our aim was to clarify the pharmacology of GLP-1R in the context of these new structural data.EXPERIMENTAL APPROACH
The affinities of GLP-1, Ex4 and various analogues were measured at human and rat GLP-1R (hGLP-1R and rGLP-1R, respectively) and various receptor variants. Molecular dynamics coupled with in silico mutagenesis were used to model and interpret the data.KEY RESULTS
The membrane-tethered NTD of hGLP-1R displayed similar affinity for GLP-1 and Ex4 in sharp contrast to previous studies using the soluble isolated domain. The selectivity at rGLP-1R for Ex4(9–39) over Ex4(9–30) was due to Ser-32 in the ligand. While this selectivity was not observed at hGLP-1R, it was regained when Glu-68 of hGLP-1R was mutated to Asp.CONCLUSIONS AND IMPLICATIONS
GLP-1 and Ex4 bind to the NTD of hGLP-1R with similar affinity. A hydrogen bond between Ser32 of Ex4 and Asp-68 of rGLP-1R, which is not formed with Glu-68 of hGLP-1R, is responsible for the improved affinity of Ex4 at the rat receptor. 相似文献78.
Stephanie C. Licata Donna M. Platt John R. Atack Gerard R. Dawson Michael L. Van Linn James K. Rowlett 《Neuropharmacology》2010,58(2):357-193
Previous reports suggest that γ-aminobutyric acid type A (GABAA) receptors containing α1 subunits may play a pivotal role in mediating the discriminative stimulus effects of benzodiazepines (BZs). L-838,417 (7-tert-Butyl-3-(2,5-difluoro-phenyl)-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine) is a GABAA receptor modulator with intrinsic efficacy in vitro at α2, α3, and α5 subunit-containing GABAA receptors, and little demonstrable intrinsic efficacy in vitro at α1 subunit-containing GABAA receptors. The present study evaluated the discriminative stimulus effects of L-838,417 in order to determine the extent to which the α2, α3, and α5 subunit-containing GABAA receptors contribute to the interoceptive effects of BZ-type drugs. Squirrel monkeys (Saimiri sciureus) were trained to discriminate L-838,417 (0.3 mg/kg, i.v.) from vehicle under a 5-response fixed-ratio schedule of food reinforcement. Under test conditions, L-838,417 administration resulted in dose-dependent increases in drug-lever responding that were antagonized by the BZ-site antagonist, flumazenil. Administration of non-selective BZs, compounds with 10-fold greater affinity for α1 subunit-containing GABAA receptors compared to α2, α3, and α5 subunit-containing GABAA receptors, barbiturates and ethanol (which modulate the GABAA receptor via a non-BZ site), all resulted in a majority of responses on the L-838,417-paired lever (65-100% drug-lever responding). βCCT, an antagonist that binds with 20-fold greater affinity for α1 subunit-containing GABAA receptors relative to α2, α3, and α5-containing GABAA receptors, had no significant effect on the discriminative stimulus effects of L-838,417 or the L-838,417-like effects of diazepam or zolpidem. These data suggest that efficacy at α2, α3, and/or α5 subunit-containing GABAA receptors likely are sufficient for engendering BZ-like discriminative stimulus effects. 相似文献
79.