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11.
Debora Steiner Tomer Avidor-Reiss Ester Schallmach Daniella Saya Zvi Vogel 《Journal of molecular neuroscience : MN》1996,27(2):195-203
It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed
AC superactivation (or supersensitization). More recently, we showed that acute Gi/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report
that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin
sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers)
strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation
of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced
superactivation of AC types I and VIII. 相似文献
12.
Magí Farré María-Teresa Terán Pere N. Roset Marta Mas Marta Torrens J. Camí 《Psychopharmacology》1998,140(4):486-495
Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males
with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized
clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam
0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple
reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects
questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales
(VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest
doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases
in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related
effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria
in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest
that it may be included in the group of benzodiazepines with a relatively high abuse potential.
Received: 13 February 1998/Final version: 1 May 1998 相似文献
13.
Myung Ha Yoon Kyung Deok Park Hyung Gon Lee Woong Mo Kim Tae Hoon An Yeo Ok Kim Lan Ji Huang Cui Jin Hua 《Journal of Korean medical science》2008,23(6):1033-1038
The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 µL of 5% formalin solution was applied to the hind-paw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level. 相似文献
14.
H. Ehrenreich C. Kolmar C. Pittius F. -D. Goebel 《Journal of molecular medicine (Berlin, Germany)》1988,66(4):175-180
Summary Administration of synthetic human corticotropin-releasing factor (hCRF, 2 µg/kg body weight) during simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) produced a significant increase in plasma C-peptide levels of six male Type 2 diabetic patients which even exceeded the postprandial values. This stimulatory effect of hCRF/naloxone on plasma C-peptide was less pronounced in six healthy men. hCRF alone did not provoke any reaction of plasma C-peptide in either group.The possibility of a paracrine, CRF-dependent mechanism in pancreatic islets which somehow involves inhibitory opioid receptors is preferentially discussed. Such a mechanism may underlie the stimulatory action of hCRF/naloxone on B cells and would explain the absent reaction of peripheral venous plasma C-peptide to hCRF alone as well as the amplifying effect of simultaneous opioid receptor blockade.Abbreviations ACTH
adrenocorticotropic hormone
- C-peptide
connecting-peptide
- CRF
corticotropin-releasing factor
- hCRF
human CRF
- oCRF
ovine CRF
- min
minutes
- S.D.
standard deviation
- S.E.M.
standard error of the mean
This study was supported by the Deutsche Forschungsgemeinschaft (Go 299/3-2)Dedicated to Professor Dr. N. Zöllner on the occasion of his 65th birthday 相似文献
15.
Gertrud Koch Klaus Wiedemann Hansjörg Teschemacher 《Naunyn-Schmiedeberg's archives of pharmacology》1985,331(4):351-354
Summary Opioid activities of human -casomorphin-4,-5,-7 and -8 and, for comparison, of the corresponding bovine -casomorphins were studied in the guinea-pig ileum preparation. Binding parameters, i.e. K
d
-values and binding site concentrations, for the interaction of human and bovine -casomorphins with opioid receptors in rat brain homogenates were determined in inhibition experiments, using [3H]-(d-Ala2, MePhe4, Gly-ol5)enkephalin, [3H]-(d-Ala2, d-Leu5)enkephalin and [3H]ethylketazocin as -, - and -opioid receptor ligands. Analysis of binding data was performed using a non-linear curve fitting program. All -casomorphins examined displayed opioid activity. The affinity was highest for -receptors, less so for -receptors and lowest for -receptors. It is suggested that human -casomorphins might play a role as food hormones. 相似文献
16.
Summary The longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum has been employed for the study of the effect of pertussis toxin (IAP) on opioid dependence. Guinea-pigs were treated with IAP (120 g/kg, i.p.) either prior to chronic administration of an opioid or after opioid dependence had been established. The isolated preparations were tested in vitro for dependence; that is, the naloxone-precipitated withdrawal contracture. Naloxone almost failed to evoke a sign of dependence in preparations treated with IAP prior to chronic exposure to an opioid. In contrast, IAP failed to affect the withdrawal contracture when applied to an animal after dependence has been established. It is concluded that theN
i-unit, the substrate for IAP, plays a critical function in the development of dependence. The continuous activation of the opioid receptor associated with the development of dependence may induce changes inN
i which in turn prevent the interaction of IAP with its substrate. 相似文献
17.
The analgesic effect, of intracerebroventricular administration of morphine, ketocyclazocine, [D-ala2]-methionine enkephalinamide (DAM), [D-ala2-D-leu5]-enkephalin. (DADLE), leuenkephalin, metenkephalin, and -endorphin on acetic acid-induced abdominal writhing (AAW) was investigated in naive and morphine-tolerant mice. It was found that the relative potencies of a series of opioids are different in naive and morphine-tolerant groups. In naive animals, the order of potency (ED50, nmol) was -endorphin > morphine=DAM > DADLE > ketocyclazocine=leuenkephalin=metenkephalin. The morphine-tolerant animals were cross-tolerant to ketocyclazocine and to all the peptides studied; DAM and -endorphin exhibited the highest degree of tolerance. In morphine-tolerant animals, the order of potency was morphine=DADLE=-endorphin > DAM=ketocyclazocine =metenkephalin > leuenkephalin. The results indicate that endogenous opioid systems may be affected by tolerance development to morphine. 相似文献
18.
The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). -Endorpin, d-Met2, Pro5-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of - and -receptors in mediation of the analgesic effect induced by different types of opioids. 相似文献
19.
20.