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41.
Toxicity of cyclosporine (CsA), an immunosuppressive drug widely used in transplantation, to the transplanted kidney creates a serious side effect. Therefore, searching for sensitive indicators of nephrotoxic action is well worth the effort. In this work we decribe the results of estimation of urine concentration of lysosomal enzymes widely present in the kidney: N-acetyl--D-glucosaminidase (NAG), its isoenzyme NAG-B and -glucuronidase (-Gr). The studies were conducted in various periods after transplantation of kidneys, on patients under various treatments and receiving different doses of CsA. The results indicate a substantial dependence of the activity of NAG and NAG-B on CsA doses and the period after transplantation. The enzyme proved to be also a sensitive indicator of graft rejection. No such dependence was observed in the case of -Gr. 相似文献
42.
We describe the separation of alanylaminopeptidase (AAP) from urine into two isoenzymes: a particulate and a soluble form. The separation was accomplished using ion-exchange column chromatography on DEAE-52 cellulose. The purity of the isolated forms was confirmed electrophoretically. We attempted to create a method allowing the quantitative assessment of AAP isoenzymes in urine based on electrophoretic separation in 7.5% polyacrylamide gel with subsequent densitometric analysis. The content of AAP isoenzymes in examined urine was estimated using ultracentrifugation. The differences in the content of cytosolic and microsomal forms were observed suggesting the possibilities of using AAP isoenzymes in diagnostics. Furthermore, the effect of temperature on the activity of AAP separated on DEAE-52 cellulose was studied. 相似文献
43.
Keenan RM Callahan JF Samanen JM Bondinell WE Calvo RR Chen L DeBrosse C Eggleston DS Haltiwanger RC Hwang SM Jakas DR Ku TW Miller WH Newlander KA Nichols A Parker MF Southhall LS Uzinskas I Vasko-Moser JA Venslavsky JW Wong AS Huffman WF 《Journal of medicinal chemistry》1999,42(4):545-559
Previously, we reported the direct design of highly potent nonpeptide 3-oxo-1,4-benzodiazepine fibrinogen receptor antagonists from a constrained, RGD-containing cyclic semipeptide. The critical features incorporated into the design of these nonpeptides were the exocyclic amide at the 8-position which overlaid the Arg carbonyl, the phenyl ring which maintained an extended Gly conformation, and the diazepine ring which mimicked the gamma-turn at Asp. In this paper, we investigate conformational preferences of the 8-substituted benzodiazepine analogues by examining structural modifications to both the exocyclic amide and the seven-membered diazepine ring and by studying the conformation of the benzodiazepine ring using molecular modeling, X-ray crystallography, and NMR. We found that the directionality of the amide at the 8-position had little effect on activity and the (E)-olefin analogue retained significant potency, indicating that the trans orientation of the amide, and not the carbonyl or NH groups, made the largest contribution to the observed activity. For the diazepine ring, with the exception of the closely analogous 3-oxo-2-benzazepine ring system described previously, all of the modifications led to a significant reduction in activity compared to the potent 3-oxo-1, 4-benzodiazepine parent ring system, implicating this particular type of ring system as a desirable structural feature for high potency. Energy minimizations of a number of the modified analogues revealed that none could adopt the same low-energy conformation as the one shared by the active (S)-isomer of the 3-oxo-1, 4-benzodiazepines and 3-oxo-2-benzazepines. The overall data suggest that the features contributing to the observed high potency in this series are the orientation of the 3-4 amide and the conformational constraint imposed by the seven-membered ring, both of which position the key acidic and basic groups in the proper spatial relationship. 相似文献
44.
Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg
TPA) protocols were found to be under multigenic control. Eighty- one N2
mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were
either solidly resistant (no papillomas) or highly susceptible (> or = 7
papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite
markers to check for associations with susceptible and resistant
phenotypes. A locus on Chr 5 (Skts4) was found to control the
susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to
papilloma formation. In addition, higher than expected linkage scores were
seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is
required to establish whether genes determining papilloma formation are
located in these regions of the genome. In general, no evidence was seen
for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in
17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.
相似文献
45.
研究生作为PBL指导教师在药理学教改中的探索 总被引:1,自引:0,他引:1
药理系首次进行聘用研究生作为PBL指导教师的教改尝试,深刻体会到其重要性所在。研究生具有知识面宽、概念清楚、基础知识扎实等诸多优势,有利于提高本科生的教学质量。药理系组织研究生参加教学培训、开展讨论、吸纳有益的建议;提高研究生对PBL教学的重视程度、消除研究生顾虑;争取研究生导师的大力支持;并由教授亲自检查并督促研究生教学工作。作为PBL教学指导教师,研究生是学生与任课教授、讲师之间的中介人和桥梁,有利于提高学生的综合素质、教师教学水平。 相似文献
46.
47.
R W Olson D S Cohen E C Ku E F Kimble H B Renfroe E F Smith 《European journal of pharmacology》1987,133(3):265-273
CGS 15435A, a novel thromboxane (Tx) synthetase inhibitor (5-chloro-1-methyl-2-(3-pyridyl)-3-indolhexanoic acid HCl), had a selectivity for Tx synthetase 100,000-fold greater than that for cyclooxygenase, PGI2 synthetase and lipoxygenase enzymes. In conscious beagles, 1 h following a single 3 mg/kg p.o. dose, serum TxB2 was inhibited 95% by CGS 15435 and 82% by dazoxiben (DAZ). Unlike the short acting Tx synthetase inhibitor DAZ, CGS 15435A significantly inhibited TxB2 formation 4, 6, 12 and 24 h after dosing. Serum levels of 6-keto PGF1 alpha and PGE2 were significantly increased following the administration of either drug. CGS 15435A and DAZ were further examined in a model with known Tx involvement. Thrombotic sudden death, produced in anesthetized rabbits by injection of 0.75 mg/kg arachidonic acid (AA) i.v. resulted in a 45% fall in the platelet count and 0% survival. Pretreatment with DAZ (8.6 mumol/kg i.v.) at 0.25 or 2 h pre-AA resulted in 3 and 42% thrombocytopenia and 100 and 0% survival respectively. CGS 15435A (8.6 mumol/kg i.v.) prevented the increases in plasma TxB2 levels, thrombocytopenia and sudden death with pretreatment at 0.25 h (0% thrombocytopenia and 100% survival) or 24 h (11% thrombocytopenia and 83% survival) before AA. These data indicate that CGS 15435A is a potent and selective Tx synthetase inhibitor with a long duration of action, and suggest that the compound could be useful in chronic, non-symptomatic indications of Tx involvement. 相似文献
48.
目的了解笔者所在医院2008年度临床感染病原菌的菌种分布及其耐药现状。方法用VITEK微生物自动鉴定仪鉴定菌种,纸片扩散法检测临床分离菌对各种抗菌药物的敏感性,判读标准参照当年的CLSI M100文件。结果临床分离的1900株病原菌中革兰阴性杆菌、革兰阳性球菌和真菌所占比例分别为68.42%、18.16%和12.32%。分离率最高的五种病原菌:铜绿假单胞菌、大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌和白色假丝酵母菌,占所有分离病原菌的59.26%,排前20位的病原菌则占到近90%(89.63%)。革兰阴性杆菌仅对亚胺培南、头孢哌酮/舒巴坦、美洛培南、哌拉西林/他唑巴坦的平均耐药率低于30%,铜绿假单胞菌和鲍曼不动杆菌对亚胺培南、美洛培南的耐药率分别28.9%、32.9%和11.6%、24.7%,大肠埃希菌、肺炎克雷伯菌和奇异变形杆菌的ESBL阳性率分别是52.8%、37.2%和34.6%,金黄色葡萄球和凝固酶阴性葡萄球菌中耐甲氧西林株各占44.0%和60.0%,未检出万古霉素中介或耐药的葡萄球菌,检出万古霉素耐药的粪肠球菌和屎肠球菌各1株。念珠菌对氟康唑耐药率接近5%。结论临床感染病原菌构成变化不大,但真菌检出率逐年升高。非发酵菌耐药率最低的是头孢哌酮/舒巴坦,肠杆菌科耐药率最低的是亚胺培南,ESBL的阳性率逐年升高。加强病原菌及其耐药性检测和监测,对病原学诊断及指导合理选用抗生素具重要参考价值。 相似文献
49.
50.