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61.
Matosiuk D Fidecka S Antkiewicz-Michaluk L Lipkowski J Dybala I Koziol AE 《European journal of medicinal chemistry》2002,37(9):761-772
Synthesis and pharmacological activity of 1,6-diaryl-5,7(1H)dioxo-2,3-dihydroimidazo-[1,2-a][1,3,5]triazines (C) are presented. The title compounds were obtained from 1-arylimidazolinurea derivatives in cyclization reaction with difunctional carbonyl reagents--phosgene (method I) or carbonyldiimidazole (CDI) (method II). Their molecular structures were confirmed by the X-ray analysis of 1-phenyl-6-(4-chlorophenyl)-5,7(1H)-dioxo-2,3-dihydroimidazo[1,2-a][1,3,5]triazine (C2) crystals. Compounds C exhibited significant depressive action on the central nervous system (CNS) of the laboratory animals, correlated with very low acute toxicity (LD(50) > 2000 mg kg(-1) i.p.), and showed antinociceptive activity in behavioural models. Reversion of this effect by small dose of naloxone (5 mg kg(-1)) can suggest opioid-like mechanism of antinociception produced by these and other carbonyl derivatives of 1-aryl-2-iminoimidazolidine. Additionally, an effect on the serotonin neurotransmission pathway was also observed. The receptor mechanism of activity for investigated compounds was confirmed only for the opioid mu receptor in binding affinity assay test. Same tests performed for the serotonin 5-HT(2) and benzodiazepine BZD receptors showed no affinity for tested compounds. The opioid-like and serotonergic activities are similar to these described earlier for chain carbonyl 1-aryl-2-iminoimidazolidine derivatives containing urea moiety, mainly due to similar chemical structure, although compounds C are not able to adopt any of the higher energy conformations of urea derivatives. Rigid location of aromatic ring (Ar') at N6, acting as a spacer blocking any direct access to the carbonyl groups (e.g. through the hydrogen bonding), could be responsible for lack of affinity toward 5-HT(2) expressed in the binding assay test. 相似文献
62.
Matosiuk D Fidecka S Antkiewicz-Michaluk L Dybala I Koziol AE 《European journal of medicinal chemistry》2002,37(10):845-853
Synthesis and pharmacological activity of 1-aryl-5,6(1H)dioxo-2,3-dihydroimidazo[1,2-a]imidazoles (D) are presented. The title compounds were obtained from 1-aryl-2-iminoimidazolidines (1) by cyclization reaction with oxalic acid derivatives-ethyl ester (2) or chloride (3). They were tested for pharmacological activity in animal and binding assay tests. With moderate acute toxicity (LD(50) approximately 200 mg kg(-1), i.p.), they exhibited significant analgesic and serotonergic activities as results of the 'writhing' and the 'hot plate' tests indicated, and reduced number of 'head twitch' episodes after 5-HTP (5-hydroxytryptophan) administration. Reversion of the antinociception produced in the 'writhing' test by small dose of naloxon (5 mg kg(-1)) can suggest an opioid-like mechanism of their analgesic activity. The probable receptor inhibition mechanism of their analgesic and serotonergic activity was confirmed in the binding assay tests (by radioligand displacement) toward the opioid mu and serotonin 5-HT(2) receptors. Additionally, they exhibited affinity toward the benzodiazepine (BZD) receptor as well, although in behavioral tests compounds did not produce any clear depressive effect on the central nervous system (CNS) of mice. Simple chemical structure of the title compounds, in comparison to other carbonyl derivatives of 1-aryl-2-iminoimidazolidine presented in this series of papers, underline very important role both of a hydrophobic moiety (aromatic ring) and polar groups (hydrogen-bond acceptors) in the serotonin receptor interaction. The co-existence of opioid-like, serotonergic and BZD receptor inhibition activity can be very interesting and can lead to creation of the novel group of antidepressants. 相似文献
63.
We investigated the effects of a potent neurotoxin, trimethyltin (TMT), on mixed neuronal/glial cultures derived from rat hippocampal dentate gyrus. We found that TMT induced neuronal cell death in a concentration dependent manner, which was estimated by microtubule degeneration, hematoxylin histological staining and the TUNEL method. This cell death is most probably of an apoptotic type as suggested by Hoechst staining. In parallel to studies the effects of TMT on neurons, its concentration dependent actions on astroglia and microglia were also examined using GFAP and GS-B4 isolectin as immunocytochemical markers, respectively. We found that neurotoxic concentrations of TMT evoked astrocytic swelling, whereas low, non-cytotoxic concentrations caused changes in microglia morphology characteristic of their active form. The combined results of our studies provide new data concerning the cell type-specific influence of TMT and indicate that the culture of dentate gyrus cells is a feasible in vitro modelforfurther studies of neuronal-glial interaction in response to toxic injury. 相似文献
64.
65.
Shantha L. KOSARAJU Deanne LABBETT Michelle EMIN Izabela KONCZAK Leif LUNDIN 《Nutrition & Dietetics》2008,65(S3):S48-S52
There is a growing demand for delivery of antioxidants through functional foods with the concomitant challenge of protecting their bioactivity during food processing and subsequent passage through the gastrointestinal tract. This study focuses on the retention of antioxidant activity of polyphenolic antioxidants after encapsulation/spray-drying. The polyphenolic compounds present in grape-seed extract (GSE), apple polyphenol extract (APE) and olive-leaf extract (OLE) were analysed by chromatographic methods. Catechin, epicatechin and gallic acid were identified in GSE and APE. Oleorupein is the major compound found in OLE. Total polyphenol content was found to be the highest in APE followed by GSE and OLE. These extracts were encapsulated using protein-lipid emulsions and subsequently spray-dried. Optical microscopy and particle size distribution analysis indicated the sphericity and uniform size distribution pattern of the dry particles. Radical scavenging activity studies demonstrated significant retention of antioxidant activity after the encapsulation and spray-drying process. 相似文献
66.
67.
Skin surface has an acidic pH, whereas the body's internal environment maintains a near-neutral pH. The physiological role of the 'acidic mantle' and the function of the pH gradient throughout the stratum corneum remain unexplained. The pH gradient has been suggested to activate enzymes responsible for the maintenance of the skin barrier function and to facilitate the desquamation process in the stratum corneum. The aim of the study was to investigate the influence of pH of a moisturizing cream on barrier recovery in surfactant-damaged human skin. Volunteers had their skin damaged with sodium lauryl sulphate and treated those areas with the cream, adjusted to either pH 4.0 or 7.5. The study did not prove the superiority of a cream of pH 4.0 to a cream of pH 7.5 regarding promotion of skin barrier recovery, since no significant differences (p > 0.05) were found in transepidermal water loss, blood flow and skin capacitance between the treated areas. 相似文献
68.
Kosmider B Wojcik I Osiecka R Bartkowiak J Zyner E Ochocki J Liberski P 《Investigational new drugs》2005,23(4):287-297
Lung cancer remains one of the most common causes of cancer-related death worldwide. Approximately 80% is histologically non-small cell lung carcinoma (NSCLC) and in about 70% of patients it is an unresectable type. Clinical studies indicated that application of platinum derivatives caused good results and combinations of platinum with other agents could improve median survivals. In view of the central problem of sufficient efficiency of drugs in chemotherapy, efforts have focused on the development of alternative platinum-based analogues that can be more effective in cancer treatment. cis-bis(3-aminoflavone)dichloroplatinum(II) (cis-Pt(II) complex of 3-aminoflavone) represents a novel class of platinum-based potential antitumour agents. In order to evaluate the degree of apoptosis, acridine orange/ethidium bromide and Hoechst 33258/propidum iodide double staining as well as RT-PCR (P53 and BAX expression evaluation) were used in lung cancer cell line A549 after treatment with this compound in comparison with cis-diamminedichloroplatinum(II) (cis-DDP). Apoptotic cells at early and late stages and also necrotic ones were observed after usage of cis-Pt(II) complex of 3-aminoflavone and the percentage of these cells outnumbered the values obtained after cis-DDP application. The former compound induced a higher percentage of P53 and BAX expression in A549 cells in comparison with the latter one. Results indicate the beneficial properties of cis-Pt(II) complex of 3-aminoflavone as a potential antitumor drug. 相似文献
69.
Piotr?DylewiczEmail author Slawomira?Borowicz-Bienkowska Ewa?Deskur-Smielecka Piotr?Kocur Izabela?Przywarska Malgorzata?Wilk 《Zeitschrift fur Gesundheitswissenschaften》2005,13(6):313-317
A low level of physical activity and decreased exercise capacity are independent risk factors for cardiovascular and all-cause mortality. The assessment of the level of physical activity and its improvement following preventive procedures is methodologically difficult. In population studies, subjective methods, such as questionnaires, activity records and other somewhat imperfect measures (accelerometers, pedometers, and pulse monitors), are used. Direct and especially indirect assessment of physical capacity with exercise tests has become increasingly more accessible and cheap. Both methods have been proved to have high prognostic value. Assessment of physical capacity enables objectification of information on the level and effects of a subjects physical activity acquired via a questionnaire. Taking into account the above-mentioned issues, the role of the assessment of exercise capacity and its improvement is not adequately appreciated. Routine evaluation of exercise capacity has not been included in the current statements on epidemiology and prevention, even in those with an increased Framingham or SCORE risk index in whom low exercise tolerance has been proved to have an unfavorable influence on prognosis. The importance of an increase in the level of physical activity resulting in an improvement in exercise capacity in different population groups should be verified in the near future, but in our opinion there is indirect but strong evidence that actions to improve exercise capacity should become the main goals in the prevention of cardiovascular and all-cause mortality, such as cessation of cigarette smoking, body weight reduction, correction of lipid and carbohydrate metabolism disturbances, and a decrease in blood pressure. 相似文献
70.
Derdowska I Prahl A Kowalczyk W Janecki M Melhem S Trzeciak HI Lammek B 《European journal of medicinal chemistry》2005,40(1):63-68
In this study, we described the synthesis and some pharmacological properties of four new analogues of arginine vasopressin (AVP). Two peptides are substituted in position 2 with L-1-naphthylalanine (L-1-Nal) or its D-enantiomer and in position 4 with valine. In the further two compounds, we combined the above modifications with placement into position 1 of 3-mercaptopropionic acid residue (Mpa). All new peptides were tested for vasopressor and antidiuretic activities. We also estimated the uterotonic activities of these compounds in vitro. Urine samples prior and after peptide administration were analyzed for electrolytes excretion. All analogues are potent oxytocin antagonists. One of them, namely [L-1-Nal2,Val4]AVP, which appears practically not to interact with V1a and V2 receptors, is exceptionally selective. Our results open new possibilities for the design of very potent and selective oxytocin antagonists in vitro. 相似文献