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21.
Familial dysbetalipoproteinemic subjects with the E3/E2 phenotype exhibit an E2 isoform with only one cysteine residue 总被引:2,自引:0,他引:2
Maruke Smit Peter de Knuff Rune R. Frants Eduard C. Klasen Louis M. Havekes 《Clinical genetics》1987,32(5):335-341
Most familial dysbetalipoproteinemic patients are E2/E2 homozygotes for the apolipoprotein E (apoE) polymorphism, whereas patients with the E4/E2 or E3/E2 phenotype are very rare. Three out of 41 dysbetalipoproteinemic patients from our lipid clinic appeared to be E3/E2 heterozygotes. ApoE protein phenotyping and DNA oligonucleotide hybridization techniques showed that all three patients exhibit an uncommon E2 variant that contains only one cysteine residue. These results suggest that, in contrast to the by far most frequently occurring E2(Arg158----Cys) allele, heterozygosity for this uncommon E2 allele may cause familial dysbetalipoproteinemia. Preliminary family studies suggest that this uncommon E2 allele cosegregates with familial dysbetalipoproteinemia. 相似文献
22.
Cystamine, an inhibitor of transglutaminases, slows progression of Huntington's disease in the murine model by approximately 20%. Cysteamine, the dimer of cystamine, is an orphan drug approved for the treatment of nephropathic cystinosis and has a similar benefit in the murine model but with a narrower therapeutic window. In a single-center open-label study, we determined the maximum tolerable dose (MTD) and side effects of cysteamine in people with Huntington's disease. Cysteamine was started at a dose of 10 mg/kg per day, divided into four doses, and increased by 10 mg/kg per day weekly until the development of intolerable side effects or a maximum dose of 70 mg/kg per day. Of the 9 subjects, 1 had an MTD of 10 mg/kg per day, 1 had an MTD of 20 mg/kg per day, the maximum dose was 30 mg/kg per day for 2, 40 mg/kg per day for 2, and 50 mg/kg per day for 3. Dose-limiting side effects were motoric impairment in 5 and nausea in 4. The dose found tolerable by 8 of the subjects was 20 mg/kg per day. All had a noticeable hydrogen sulfide odor at doses of 40 mg/kg per day or higher. We conclude that, at a dose of 20 mg/kg per day, cysteamine was tolerable in people with Huntington's disease. Nausea and motoric impairment were the dose-limiting side effects. 相似文献
23.
为了研究半胱胺对动物生长和安全性的长期影响,分别对大鼠以0,20,35,50mg/kg注射半胱胺,以及以0,15,30,60mg/kg饲喂添加半胱胺.试验发现:每天注射20mg/kg半胱胺(以体重计)1周能明显提高大鼠的增重(P〈0.05),而其他组与对照组差异不显著(P〉0.05),而1周后的增重与对照组差异不显著;注射半胱胺11天,大鼠血液生长激素水平没有提高.在饲料中添加30mg/kg半胱胺,第1周显著提高大鼠增重(P〈0.05),而其他组与对照组差异不显著(P〉0.05);1周后添加半胱胺的各组大鼠增重均没有提高;各组大鼠的肝脏、脾脏和肾脏指数差异不显著;血液中谷丙转氨酶有所降低,而谷草转氨酶和碱性磷酸酶没有影响.实验结果表明:腹腔注射和饲料添加半胱胺对大鼠的促生长作用均是短期的,即在1周之内有促进生长作用,长期添加或注射半胱胺不能显著提高大鼠增重.在本试验的时间和剂量范围内,半胱胺对大鼠的器官形态和功能没有表现出异常影响. 相似文献
24.
Depletion of striatal somatostatin by local cysteamine injection 总被引:1,自引:0,他引:1
Local injection of cysteamine into rat striatum resulted in a dose-dependent reduction in somatostatin-like immunoreactivity (SLI). The effect was seen at 1 h, and persisted for up to 72 h, but was reversible at 1 week. The maximal depletion of SLI was approximately 50%. Histologic damage was largely confined to the needle tract. Of interest was a depletion of SLI in the contralateral striatum beginning at 3 h and maximal at 72 h. Cysteamine induced depletion of striatal SLI was not accompanied by alterations in dopamine or serotonin metabolism. Cysteamine is a useful pharmacologic tool for local somatostatin depletion. 相似文献
25.
半胱胺对小鼠疼痛感受的影响 总被引:1,自引:0,他引:1
INTRODUCTION Cysteamine (β-mercaptoethylamine) is a thiol com-pound whose biological activities have recently receivedgreat attention, and that can be found in animals whenacetyl coenzyme A is hydrolized by pantethinase.Clinically it has been used in the treatment ofacetaminophen poisoning and in the treatment ofnephropathic cystinosis. It was reported that cys-teamine depletes somatostatin in the stomach, duodenum,pancreas, gut and hypothalamus of rat. Cysteaminewas also found to deplete somatostatin in the brain 相似文献
26.
Dr. Gordon L. Kauffman Jr. MD Elizabeth Kolve BS Shlomo Walfisch MD John Mangus 《Digestive diseases and sciences》1988,33(6):667-672
The purposes of this study were to determine whether inhibition of cyclooxygenase is a mechanism by which cysteamine and mepirizole produce duodenal ulcers, identify qualitative or quantitative differences in prostanoid production between gastric mucosa and duodenum, and determine whether differences in cyclooxygenase sensitivity to inhibition by aspirin exist between these two tissues. In fed female rats, gastric mucosal prostaglandin E2 (PGE2) and prostacyclin (PGI2) generation was 235±25 and 832±40 ng/g/min, respectively, whereas full-thickness duodenal PGE2 and PGI2 generation was 665±46 and 662±49 ng/g/min, respectively. Over an intraperitoneal dose range of 0– 25 mg/kg, aspirin-induced cyclooxygenase inhibition was dose-dependent and similar for the two tissues. Duodenal ulceration (16.7 mm2) produced by cysteamine, 425 mg/kg, was associated with a 46% reduction in duodenal PGE2 generation, while having no effect on PGI2 generation; however, cysteamine, 213 mg/kg, produced no visible duodenal mucosa injury yet reduced duodenal PGE2 generation 39% compared to control values. In fed male rats, gastric mucosal PGE2 and PGI2 generation was 179± 18 and 813± 61 ng/g/min, respectivley, whereas duodenal PGE2 and PGI2 generation was 321± 27 and 454± 38 ng/g/min, respectively. Duodenal ulceration (7.7 ± 2.3 mm2) produced by oral mepirizole was associated with a 63% reduction in duodenal PGE2 generation compared to control values, while having no effect on PGI2 generation. Subcutaneous aspirin, 100 mg/kg, which reduced duodenal PGE2 generation to a greater degree than either ulcerogen, given in conjunction with pentagastrin, did not produce visible duodenal ulceration. It therefore seems unlikely that reduced PGE2 generation within the duodenum is the primary mechanism of gross injury associated with these two ulcerogens.Supported by grant AM 17328 from NIADDK. 相似文献
27.
28.
Komei Washino Lynne Katsikas Wolfram Schnabel 《International journal of radiation biology》2013,89(6):747-758
SummaryPoly(riboadenylic acid) was irradiated in N2O-saturated dilute aqueous solution at pH 7·8 with single pulses (50–200 ns) of 16 MeV electrons. With the aid of Rayleigh light scattering measurements both the extent and rate of main-chain scission were measured in the absence and the presence of cysteamine (RSH). In both cases two modes of light scattering intensity (LSI) decrease were detected. From this finding it was concluded that two chemically different radical sites, giving rise to main-chain breakage, were produced by OH attack on the macromolecules. Cysteamine reduced the extent of LSI decrease and accelerated the rate of the slow mode of LSI decrease significantly. The fast mode of the LSI decrease is due to fragment diffusion and therefore the influence of cysteamine on the rate of decay of the short-lived radical could not be studied. The assessment of the relative importance of ·OH scavenging (RSH + ·OH → RS· + H2O) and of repair (PA· + RSH → PAH + RS·) with respect to protection yielded the following: in the case of the long-lived radical, repair contributes significantly at low RSH concentration (< 10?4 m); in the case of the short-lived radical, OH scavenging dominates and repair becomes noticeable only at [RSH] > 10?4 m. The following data were evaluated in this work: 100 eV-yield of main-chain scission, G(sb) = 1·1; lifetimes of radicals: < 50 µs (short-lived), 0·6s (long-lived), kpa· + rsh = 3·4 × 106 m?1 s?1 (for long-lived radicals). 相似文献
29.
SummaryThe survival of various E. coli K12 strains with defects in the rec system have been measured after γ-irradiation in air in the presence (0·1 mol dm?3) or in the absence of cysteamine. The results confirm those of Bresler et al. (1978) indicating that the protection by cysteamine in the presence of oxygen is due to an influence on enzymatic repair. The low protection by cysteamine of wild-type cells pretreated with chloramphenicol which prevents protein synthesis, supports the above conclusion. The reason for the absence of a protective effect by OH radical scavenging and H-atom donation is discussed. It is proposed that DNA peroxyl radicals are formed during irradiation in the presence of oxygen and that they are transformed into hydroperoxides by H-atom donation from the intracellular glutathione and the added cysteamine. These hydroperoxides are still dangerous for the cell as indicated by the protective action of glutathione peroxidase observed by Marklund et al. (1984). 相似文献
30.