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1.
稳定性核素测定大鼠小肠蛋白质合成 总被引:2,自引:1,他引:1
目的:建立稳定性核素([L-^15N]亮氨酸)测定大鼠小肠蛋白质合成率的方法。方法:分别测定静脉注射相同剂量[L-^15N]亮氨酸不同时相的大鼠小肠^15N丰度及不同剂量[L-^15N]亮氨酸同一时相的大鼠小肠^15N丰度。结果:大鼠小肠游离氨基酸池中^15N核素丰度在注射后0.5h内呈线性上升并达高峰,维持4h后缓慢下降,小肠蛋白质中的^15N丰度0.5h至12h基本维持不变;随着注射剂量的增加,大鼠小肠蛋白质分数合成率(FSR)亦增加,当[L-^15N]亮氨酸剂量在1.0mmol/kg以上,FSR并不随施加[L15N]亮氨酸剂量的加大而增加。结论:在进行大鼠小肠蛋白质合成率测定时,一次性静脉注射的测量最佳时限为0.5h,剂量为1.0mmol/kg。 相似文献
2.
M. Depré D. J. Margolskee A. Van Hecken J. S. Y. Hsieh A. Buntinx P. J. De Schepper J. D. Rogers 《European journal of clinical pharmacology》1992,43(4):431-433
Summary The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i. v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i. v. doses of MK-571 at weekly intervals.The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, ll-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679.The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition. 相似文献
3.
The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that ‘illness’-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found. 相似文献
4.
5.
聚—DL—乳酸复合材料的细胞毒性评价 总被引:2,自引:0,他引:2
孙皎 《口腔材料器械杂志》1998,7(2):66-67
本文对新研制的聚-DL-乳酸可吸收复合材料进行细胞毒性的实验研究,采用L-929小鼠成纤维细胞,经材料浸提液与细胞接触2、4、7 天后,在分光光度仪下测定光吸收度,以评价材料的细胞毒性.结果表明;该材料对培养细胞无明显细胞毒性刺激作用,细胞生长良好,各期实验组的细胞增殖状况与阴性对照组相似. 相似文献
6.
Iwao Kadobayashi Masahiko Mori Kunio Tanaka Akiteru Toyoshima Nobukatsu Kato 《Physiology & behavior》1980,25(2):317-320
Small doses (10 and 20 mg/kg) of L-DOPA inhibited the amplitude of the visual evoked response (VER), while large doses (40 and 80 mg/kg) enhanced it. Though low doses (12.5 and 25 mg/kg) of L-5-HTP caused a slight increase in amplitude of the VER, the simultaneous administration of 12.5 mg/kg of L-5-HTP and 10 mg/kg of L-DOPA produced a marked enhancement. The peak latency was prolonged after the injection of any doses of L-DOPA, L-5-HTP, or both. 相似文献
7.
Broiler chicks were provided choices of synthetic diets (a) adequate or low in lysine, and (b) adequate in or devoid of lysine. In each case, chicks consumed some of each diet offered, but preference was shown for the adequate lysine diet. Growth rates of chicks given choices ranged from 80% of that of chicks fed an adequate lysine diet with no choice for two weeks, then growth rates fell to about 60% of those fed adequate lysine. In another study, chicks were fed a diet devoid of lysine but were offered pure L-lysine HCl in a separate feeder. These chicks selected some of the supplementary lysine, but their body weights were only 68% of the body weight of chicks fed an adequate lysine diet after 21 days. Chicks given a choice of diets prepared with an adequate quantity of either L- or D-lysine preferred with L-lysine diet but did not select sufficient quantity to reach normal growth. These observations indicate that chicks can discern the presence of L-lysine in diets or separately, but will not select sufficient quantity for maximum growth potential. A diet prepared with D-lysine was more acceptable than one completely devoid of lysine, suggesting some sensory recognition for lysine. 相似文献
8.
D. J. Pettibone B. V. Clineschmidt V. J. Lotti G. E. Martin J. R. Huff W. C. Randall J. Vacca J. J. Baldwin 《Naunyn-Schmiedeberg's archives of pharmacology》1986,333(2):110-116
Summary L-654,284 ((2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizine-2-yl)-N-methyl-2-hydroxyethanesulfonamide) was tested in several in vitro and in vivo models for 2-adrenoceptor antagonist activity and compared to several reference agents. In vitro L-654,284 competed for the binding of 3H-clonidine or 3H-rauwolscine (K
i's 0.8 nM, 1.1 nM) and blocked the presynaptic effects of clonidine in the rat isolated vas deferens (pA2, 9.1). L-654,284 exhibited marked 2- vs. 1-adrenoceptor selectivity in vitro, inhibiting 3H-prazosin binding with a K
i of 110 nM and blocking the effects of methoxamine on the vas deferens with a pA2 of 7.5. In vivo L-654,284 at 22 nmoles/kg i.v. doubled the ED50 of clonidine to produce mydriasis in rats. Given orally, the potency of L-654,284 in this test was reduced by a factor of 5.5. L-654,284 also potently increased cerebrocortical NE turnover in the rat, another in vivo index of 2-adrenoceptor blockade in the central nervous system. In the periphery, L-654,284 demonstrated 2-adrenoceptor selectivity by preferentially blocking the pressor effects of UK 14304 versus those of methoxamine in the pithed rat. Overall, L-654,284 was generally a more potent 2-adrenoceptor antagonist than RX 781094 with comparable 2/1 selectivity and was several times more potent and 2-selective than WY 26703 or yohimbine. In addition, L-654,284 had better (5–6 times) oral bioavailability than RX 781094 or WY 26703. 相似文献
9.
H Lauder L A Sellers T -P D Fan W Feniuk P P A Humphrey 《British journal of pharmacology》1997,122(4):663
- The aim of the present study was to determine the effect of somatostatin (SRIF) on mitogen-induced regeneration of rat aortic vascular smooth muscle cells (VSMC) and for comparison Chinese hamster ovary (CHO)-K1 cells expressing human recombinant sst5 receptors (CHOsst5), following partial denudation of a confluent cell monolayer. Regeneration was assessed by measuring areas of recovery into the denuded area and by counting total cell numbers.
- In VSMC, SRIF (0.1 nM–1 μM) had no effect on the basal levels of regeneration but caused a concentration-dependent inhibition (pIC50 8.0–8.6) of the stimulated regeneration induced by sub-maximal concentrations of basic fibroblast growth factor (bFGF, 10 ng ml−1), platelet-derived growth factor-BB (PDGF, 5 ng ml−1) or endothelin-1 (ET-1, 100 nM). SRIF (pIC50 8.8) also inhibited bFGF-induced regeneration of CHOsst5 cells.
- In VSMC, the inhibitory action of SRIF on the regeneration induced by bFGF (10 ng ml−1) was due to an anti-proliferative effect, rather than an effect on cell migration, as SRIF (0.1 nM–1 μM) abolished bFGF-induced increases in total cell numbers. The bFGF-induced increase in cell numbers was also abolished by actinomycin D (0.1 μg ml−1).
- The sst5 receptor-selective agonist, L-362,855 (pIC50 10.5), was about 100 times more potent than SRIF at inhibiting bFGF-induced regeneration of both VSMC and CHOsst5 cells whilst the sst2 receptor-selective agonist, BIM-23027 (pIC50 6.8), was approximately 20 times weaker than SRIF.
- The sst5 receptor antagonist, BIM-23056 (100 nM), antagonized SRIF-induced inhibition of bFGF-induced regeneration in both VSMC and CHOsst5 cells (estimated pKB values 8.8 and 8.3, respectively).
- SRIF-induced inhibition of bFGF-induced regeneration of VSMC and CHOsst5 cells was abolished by pretreating cells with pertussis toxin (100 ng ml−1) for 20 h.
- These findings suggest that SRIF-induced inhibition of the proliferation of rat aortic VSMC is mediated via activation of receptors which are similar to human sst5 receptors. Furthermore this inhibitory effect is transduced via pertussis toxin-sensitive Gi/Go proteins.
10.
Somatostatin receptors mediating inhibition of basal and stimulated electrogenic ion transport in rat isolated distal colonic mucosa 总被引:4,自引:0,他引:4
E. S. McKeen W. Feniuk P. P. A. Humphrey 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(4):402-411
The aim of this study was to examine the potencies of several recently identified selective somatostatin (SRIF)-receptor ligands as inhibitors of electrogenic ion transport in the rat distal colonic mucosa with the view to identifying the SRIF receptor type involved. Under basal conditions, cumulative administration of SRIF and SRIF2g decreased short circuit current (SCC), a measure of electrogenic ion transport, with EC50 values of 4 nM and 9 nM respectively. The peptidase inhibitors, phosphoramidon (1 M) and amastatin (10 M), had no effect on the potencies of either SRIF or SRIF28. The inhibitory action of SRIF on basal SCC was suppressed by piretanide and diphenylamine-2-carboxylate, compatible with the assumption that the Na+K+2Cl– co-transporter and Cl– channels, respectively, may be involved in this antisecretory action of SRIF. Tetrodotoxin (1 M) had no effect on the antisecretory action of SRIF, suggesting that the process was not neuronally mediated.All of the SRIF analogues examined, with the exception of BIM-23056, maximally inhibited basal SCC to a similar extent as SRIF. Seglitide and octreotide were both more potent antisecretory agents than SRIF (respective EC50 values, 0.4 nM and 1.5 nM) suggesting that this effect was mediated by a receptor belonging to the SRIF1 receptor group. The most distinguishing feature of the rank order of agonist potencies was the high potency of the selective sst2 receptor ligand, BIM-23027 (EC50, value 0.32 nM), the weaker potency exhibited by the selective sst5 receptor ligand, L-362855 (EC50 value 21 nM), and the lack of agonist activity displayed by the selective sst3 receptor ligand, BIM-23056 (EC50 value > 1000 nM). This profile is comparable with that observed in binding studies on the recombinant sst2 receptor.Forskolin-stimulated secretion was suppressed by SRIF analogues with the rank order of agonist potencies BIM-23027 > SRIF > L-362855 > BIM-23056 which resembled that exibited under basal conditions. However, the absolute potencies of these agonists were lower (respective EC50 values 2 nM, 14 nM, 38 nM and > 1000 nM) whilst the magnitude of inhibition was about three fold greater. BIM-23027 and SRIF (both 30 nM) also inhibited carbachol-stimulated increases in basal SCC by 60–70%, while a similar concentration of L-362855 inhibited these responses by 11 %. BIM-23056 (1 M) had no effect on carbachol-simulated secretion. Radioligand binding studies on rat colonic mucosal membranes using [125I]-Tyr11-SRIF suggested heterogeneity of SRIF binding sites. Thus, SRIF and SRIF28 competed for binding (IC50 values, 0.32 and 0.63 nM, respectively) with Hill slopes less than unity; while seglitide and BIM-23027 both maximally displaced only 30–40% of specific binding with apparent high affinity (respective pIC50 values, 10.1 nM and 10.0).In conclusion, SRIF decreases basal as well as both cAMP and Ca2+-dependent Cl– secretion in rat colonic mucosa. The rank order of agonist potencies suggests that receptors resembling the recombinant sst2 receptor mediate inhibition of basal and forskolin-stimulated secretion. Radioligand binding studies suggest that BIM-23027 interacts with a sub-population of [125I]Tyr11-SRIF binding sites in rat colonic mucosal membranes which probably correspond to the receptors mediating the antisecretory effects described here. 相似文献