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排序方式: 共有125条查询结果,搜索用时 31 毫秒
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PAOLO RUZZA ANDREA CALDERAN BRUNO FILIPPI BARBARA BIONDI ARIANNA DONELLA DEANA LUCA CESARO LORENZO A. PINNA GIANFRANCO BORIN 《Chemical biology & drug design》1995,45(6):529-539
Tyrosine protein kinases (TPKs) of the src family contain two major phosphoacceptor sites which are homologous to the Tyr 416 and Tyr 527 of pp60c-src. The former represents the main autophosphorylation sites of these enzymes, and its phosphorylation correlates with increased kinase activity. It has previously been demonstrated that the Src-like tyrosine kinase expressed by the oncogene lyn displays a high affinity toward the heptapeptide H-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-OH, which reproduces the main autophosphorylation site of the Src family enzymes [Donella-Deana, A., Marin, O., Brunati, A.M. & Pinna, L.A. (1992) Eur. J. Biochem. 204 , 1159–1163]. Our study was addressed to the synthesis of some derivatives of this sequence in order to obtain both peptide substrates suitable for the detection of the Src-like tyrosine kinase activity and active site-directed inhibitors specific for this class of enzymes. For this purpose we synthesized by classical solution methods the heptapeptide and its dimeric form. Moreover, in order to improve the proteolytic resistance of these peptides we also synthesized their cyclic derivatives and their N-terminal acetylated and C-terminal amidated analogs. The correlation between the different structural properties induced by the modifications of the native sequence and the propensity of the peptides to act as Lyn substrates was examined. The kinetic data obtained indicate that the extent of the peptide phosphorylation varies considerably depending on the flexibility and length of the analogs. While the cyclization and the C-terminal amidation of the heptapeptide are detrimental for the Lyn activity, dimeric derivatives display very favourable kinetic constants. In particular the cyclic dimer is an especially suitable substrate for the tyrosine kinase and a powerful inhibitor of both the phosphorylation activity of Lyn and the enzyme autophosphorylation. © Munksgaard 1995. 相似文献
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PAOLO RUZZA ARIANNA DONELLA DEANA ANDREA CALDERAN MICHELA PAVANETTO LUCA CESARO LORENZO A. PINNA GIANFRANCO BORIN 《Chemical biology & drug design》1995,46(6):535-546
Tyrosine-specific protein kinases and phosphatases are important signal transducing enzymes in normal cellular growth and differentiation and have been implicated in the etiology of a number of human neoplastic processes. In order to develop agents which inhibit the function of these two classes of enzymes by interfering with the binding of their substrates, we synthesized analogs derived from the peptide EDNEYTA. This sequence reproduces the main autophosphorylation site of Src tyrosine kinases. In this work we report the synthesis, by classical solution methods, of the phosphotyrosyl peptide ED-NEYpTA as well as of three analogs in which the phosphotyrosine is replaced by a phosphinotyrosine and by two unnatural, non-hydrolyzable amino acids 4-phosphonomethyl-l -phenylalanine and 4-phosphono-l -phenylalanine. The Src peptide and its derivatives were tested as inhibitors of three non-receptor tyrosine kinases (Lyn, belonging to the Src family, CSK and PTK-IIB) and a non-receptor protein tyrosine phosphatase obtained from human T-cell (TC-PTP). The biomimetic analogues, which do not significantly affect the activity of CSK, PTK-IIB and TC-PTP, act:is efficient inhibitors on Lyn, influencing both the exogenous phosphorylation and, especially, its autophosphorylation. In particular, the Pphe derivative may provide a basis for the design of a class of inhibitors specific for Lyn and possibly Src tyrosine kinases, capable of being used in vivo and in vitro conditions. © Munksgaard 1995. 相似文献
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KATJA DIERCKE ISABELLE OLLINGER JUSTO LORENZO BERMEJO KATHRIN STUCKE CHRISTOPHER J. LUX MONIKA BRUNNER 《International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children》2012,22(1):60-67
International Journal of Paediatric Dentistry 2011; 22: 60–67 Background. About 11% of children and adolescents suffer from dental fear. These young people run an increasing risk of undergoing more invasive treatments. Aim. We researched the management of dental anxiety in young patients by general and paediatric dentists as well as by trained and untrained dentists. Design. Eight hundred dentists in Germany were interviewed via e‐mail regarding their experience, treatment techniques, information material and complications during the treatment of fearful children. We also examined how difficult dentists judge the treatment of anxious children and how often they participate in continuing education courses. Results. Paediatric dentists applied a greater spectrum of management techniques than general dentists. They used more often psychotherapeutic interventions and anxiety assessment questionnaires. Dentists who frequently attend in continuing education courses judged the treatment to be less difficult and also used psychotherapeutic interventions more often. Conclusions. German paediatric dentists and dentists who take continuing education courses utilise a broader range of techniques to manage dental anxiety. They may be eminently suited to treat children with severe forms of anxiety. Therefore, dentists who treat young patients should participate in education programmes so as to reduce both the anxiety of their patients and their own anxiety. 相似文献
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MASSIMO BARAVELLI M.D. PAOLO CATTANEO M.D. ANDREA ROSSI M.D. MARIA CRISTINA ROSSI M.D. CECILIA FANTONI M.D. Ph.D. ANNA PICOZZI M.D. DANIELA IMPERIALE M.D. MELANIA ROMANO M.D. LUCIA SAPORITI M.D. ALDA BREGASI M.D. LORENZO MENICANTI M.D. CLAUDIO ANZÀ M.D. 《Pacing and clinical electrophysiology : PACE》2010,33(9):1054-1062
Background: Although it has been recently demonstrated that there was no significant difference in total survival and clinical outcomes between patients who underwent coronary artery bypass grafting (CABG) with or without surgical ventricular reconstruction (SVR), the question of whether or not SVR decreases the arrhythmic risk profile in this population has not been clarified yet. Objective: To determine the real incidence of sudden cardiac death (SCD) and sustained ventricular tachycardia/ventricular fibrillation (sustained VT/VF) in patients following CABG added to SVR and to define their clinical and echocardiographic parameters predicting in‐hospital and long‐term arrhythmic events (SCD + sustained VT/VF). Methods: Pre‐ and postoperative clinical and echocardiographic values as well as postoperative electrocardiogram Holter data of 65 patients (21 female, 63 ± 11 years) who underwent SVR + CABG were retrospectively evaluated. Results: Mean follow‐up was 1,105 ± 940 days. At 3 years, the SCD‐free rate was 98% and the rate free from arrhythmic events was 88%. Multivariate logistic analysis identified a preoperative left ventricular end‐systolic volume index (LVESVI) > 102 mL/m2 (odds ratio [OR] 1.4, confidence interval [CI] 1.073–1.864, P = 0.02; sensitivity 100%, specificity 94%) and a postoperative pulmonary artery systolic pressure (PASP) > 27 mmHg (OR 2.3, CI 1.887–4.487, P = 0.01; sensitivity 100%, specificity 71%) as independent predictors of arrhythmic events. Conclusions: Our and previous studies report a low incidence of arrhythmic events in patients following SVR added to CABG, considering the high‐risk profile of the study population. A preoperative LVESVI > 102 mL/m2 and a postoperative PASP > 27 mmHg had a good sensitivity and specificity in predicting arrhythmic events. (PACE 2010; 33:1054–1062) 相似文献
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MARCELO SANMARTÍN FERNÁNDEZ LUIS ALONSO PULPÓN JUAN FRANCISCO OTEO CARMEN EXPÓSITO PINEDA ELENA ESPAÑA BARRIO IGNACIO FERNANDEZ LOZANO LORENZO SILVA MELCHOR SANTIAGO SERRANO FIZ MANUEL de ARTAZA ANDRADE 《Pacing and clinical electrophysiology : PACE》1996,19(10):1522-1523
Permanent pacemaker implantation is required in a large number of transplantation patients principally because of sinus node dysfunction of the donor atrium. The most suitable mode of pacing in these cases is still subject to controversy. We describe one case of a single lead system of VDD stimulation and sensing of the recipient atrial signal in a 32-year-old patient with posttransplant symptomatic sinus node dysfunction. Physiological adaptation of rate was achieved with recovery of normal receptor sinus node function. (PACE 1996; 19:1522–1523). 相似文献
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CHIH-MING JAMES CHIANG JANICE M. JENKINS LORENZO A. DiCARLO 《Pacing and clinical electrophysiology : PACE》1994,17(8):1373-1379
The adoption of digital signal processing (DSP) microchips for detection and analysis of electrocardiographic signals offers a means for increased computational speed and the opportunity for design of customized architecture to address real-time requirements. A system using the Motorola 56001 DSP chip has been designed to realize cycle-by-cycle detection (triggering) and waveform analysis using a time-domain template matching technique, correlation waveform analysis (CWA). The system digitally samples an electrocardiographic signal at 1000 Hz, incorporates an adaptive trigger for detection of cardiac events, and classifies each waveform as normal or abnormal. Ten paired sets of single-chamber bipolar intracardiac electrograms (1–500 Hz) were processed with each pair containing a sinus rhythm (SR) passage and a corresponding arrhythmia segment from the same patient. Four of ten paired sets contained intraatrial electrograms that exhibited retrograde atrial conduction during ventricular pacing; the remaining six paired sets of intraventricular electrograms consisted of either ventricular tachycardia (4) or paced ventricular rhythm (2). Of 2,978 depolarizations in the test set, the adaptive trigger failed to detect 6 (99.8% detection sensitivity) and had 11 false triggers (99.6% specificity). Using patient dependent thresholds for CWA to classify waveforms, the program correctly identified 1,175 of 1,197 (98.2% specificity) sinus rhythm depolarizations and 1,771 of 1.781 (99.4% sensitivity) abnormal depolarizations. From the results, the algorithm appears to hold potential for applications such as realtime monitoring of electrophysiology studies or detection and classification of tachycardias in implantable antitachycardia devices. 相似文献