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991.
M Fujita H Egawa T Miyamoto J Nakano J Matsumoto 《European journal of medicinal chemistry》1996,31(12):981-988
Diethyl 1-cyclopropyl-5,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3,6-dicarboxylate 4 as a key-intermediate was synthesized via the Dieckmann reaction. The reaction of 4 with nucleophiles proceeded regioselectively at C-5. Facile cyclization between the C-5 and C-6 side chains of the resulting products gave novel pyrroloquinolones 10 and 12 and pyrazoloquinolones 15. They were converted into a series of cyclic amino-substituted pyrroloquinolones 17–21 and pyrazoloquinolones 22–24, and their in vitro antibacterial activities were tested. 1H-Pyrrolo[2,3-f]quinolone 17a and 2H-pyrrolo[3,4-f]quinolone 21a exhibited a potent in vitro antibacterial activity. 相似文献
992.
T2毒素在灌流大鼠肠肝中的首过效应和代谢动力学 总被引:3,自引:0,他引:3
建立并用大鼠在体肠-肝灌流标本研究了T2毒素在大鼠肠肝中的首过效应和代谢转化动力学,T2毒素在大鼠肠肝中的主要代谢产物是HT2,3′-OHHT2和其葡萄糖醛酸结合物,T2毒素具有显著的肠肝首过效应,当毒素(42μg·ml~(-1))由上肠系膜动脉恒速单次灌流(8 ml·min~(-1))肠-肝标本时,穗态肝、肠抽提率分别为0.978和0.454,总有效清除率为7.91 ml·min~(-1),T2毒素在循环灌流大鼠肠-肝标本中的消除半衰期为6.5min,主要代谢产物HT2,3′-OHHT2的生成半衰期分别为8.5和38.5 min,结果表明,T2毒素经消化道中毒后,在肠和肝的首过代谢下能很快地转化为产物,因此,毒素在体内的毒效作用主要由其代谢产物表现出来。 相似文献
993.
本文利用CNDO/2研究了1-取代-7-〔(3-(乙胺基甲基)-1-吡咯烷基〕-6,8-二氟-1,4-二氢-4-氧喹啉-3-羧酸N1位不同取代基的药效构象,首次报道了以第四最低空轨道能(FUMO),超离域度、前沿电子密度等指标与N1位取代基的立体摩尔长度、最小最大宽度等结合的N1位定量构效关系,稍优于文献用经验参数UNSAT的结果,研究表明N1位的活性不仅与立体摩尔长度有关,还与电性效应有关,支持了Domagala以不饱和度参数(UNSAT)所得的结论,但UNSAT的意义不十分明确,本研究的量化指标意义很清楚。 相似文献
994.
Thomas Wlfel Aline Van Pel Vincent Brichard Jrg Schneider Barbara Seliger Karl-Hermann Meyer Zum Büschenfelde Thierry Boon 《European journal of immunology》1994,24(3):759-764
A number of cytolytic T lymphocyte (CTL) clones derived from several melanoma patients have been found to recognize a majority of melanomas from HLA-A2 patients. We have reported previously that two such CTL clones recognize a product of the tyrosinase gene that is presented by HLA-A2. Here we show that one of these CTL clones recognizes a peptide encoded by the first nine amino acids of the putative signal sequence of tyrosinase. The other CTL clone recognizes a different tyrosinase peptide corresponding to amino acids 368–376. Both peptides contain consensus motifs of HLA-A2 binding peptides. 相似文献
995.
从脾论治磺脲类降糖药继发性失效 总被引:2,自引:0,他引:2
对 64例 2型糖尿病继发磺脲类降糖药失效患者 ,在继续口服磺脲类药的基础上加用健脾中药 ,结果显效 1 5例 ,有效 3 6例 ,无效 1 3例 ,总有效率 85 .2 4% ;治疗前后血糖明显下降 ,有显著性差异 ( P<0 .0 0 1 ) 相似文献
996.
在体外试验中研究了azimexon对小鼠脾细胞增殖以及白细胞介素2(IL-2)的影响。IL-2活性采用小鼠胸腺细胞增殖法和CTLL细胞增殖法测定。结果表明:azimexon单独不能增加脾细胞增殖和产生IL-2,但对亚适量ConA或LPS诱导的脾细胞增殖和产生IL-2有明显协同作用。 相似文献
997.
Dörthe Andrea Kesper Christiana Stute Detlev Buttgereit Nina Kreisköther Smitha Vishnu Karl‐Friedrich Fischbach Renate Renkawitz‐Pohl 《Developmental dynamics》2007,236(2):404-415
During myogenesis in Drosophila embryos, a prominent adhesive structure is formed between precursor cells and fusion-competent myoblasts (fcms). Here, we show that Duf/Kirre and its interaction partners Rols7 (found in founder myoblasts and growing myotubes) and Sns (found in fcms) are organized in a ring-structure at the contact points of fcms with precursor cells, while cytoskeletal components like F-actin and Titin are centered in this ring in both cell types. The cytoplasmic protein Blow colocalizes with the actin plugs in fcms after cell adhesion. Furthermore, the requirement of additional as yet unidentified components was demonstrated by using mammalian C2C12 myoblasts. In this study, we propose that the fusion-restricted myogenic-adhesive structure (FuRMAS) is pivotal in linking cell adhesion as well as local F-actin assembly and dynamics to downstream events that ultimately lead to plasma membrane fusion. Moreover, we suggest that the FuRMAS may restrict the area of membrane breakdown. 相似文献
998.
目的 :探讨大鼠局灶性脑缺血再灌注损伤中bcl- 2及bcl-xl蛋白的表达。方法 :采用健康雄性大鼠大脑中动脉阻断 (MCAO)模型 ,阻断大脑中动脉 (MCA)血流 2h后再灌注 ,再灌注 0 .5h ,3h ,6h ,12h ,2 4h和 4 8h断头取脑后 ,进行bcl- 2、bcl-xl蛋白免疫组化染色。结果 :①Bcl- 2、Bcl-xl蛋白在脑缺血再灌注早期表达较强 ,3h - 6h达到高峰 ,2 4h~ 4 8h逐渐转阴。②bcl- 2及bcl-xl蛋白均分布在脑缺血梗死灶的周边 ,梗死中心区及正常区无表达。结论 :局灶性脑缺血再灌注损伤时 ,bcl- 2及bcl-xl表达对神经细胞的凋亡可能起着抑制作用 相似文献
999.
1000.
AIMS: Scarcity of resources, expertise and evidence-based models have so far limited delivery of patient-centred diabetes education. We have developed and validated a group care approach that is applicable to everyday clinical practice and cost-effective in improving metabolic control, knowledge of diabetes, health behaviours, and quality of life in Type 2 diabetes. A clinical trial (ROMEO) was planned to evaluate applicability and reproducibility of group care in other outpatients facilities and assess its impact on a larger patient population. METHODS: Multicentre, randomized, controlled clinical trial of group vs. individual care in the routine management of Type 2 diabetes. Nine hundred patient aged < 80, with diabetes of > or =1 year known duration, treated by either diet alone or diet and oral agents, will be recruited in 15 centres and followed for 4 years. Training of physicians, nurses and dietitians included preparation of operating manual and videos, interactive sessions, and evaluation of local facilities and resources. RESULTS: Primary measurements: 3-monthly HbA1c, fasting blood glucose, body weight, waist-hip ratio, yearly blood lipids, and bi-yearly assessment of knowledge of diabetes, health behaviours and quality of life. Secondary outcomes: systolic and diastolic blood pressure, evaluation of ECG for ischaemia and QT interval, hypoglycaemic and anti-hypertensive medication and cardiovascular events. Analysis will be by intention-to-treat. DISCUSSION: If ROMEO confirms that group care can be successfully implemented in different clinics, a novel clinico-pedagogic tool will have been acquired to support patient-centred education, improve lifestyle and outcomes, support team work, enhance providers' attitudes and competencies and ameliorate diabetes care organization. 相似文献