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121.
Ryckebusch A Deprez-Poulain R Maes L Debreu-Fontaine MA Mouray E Grellier P Sergheraert C 《Journal of medicinal chemistry》2003,46(4):542-557
Three series of monoquinolines consisting of a 1,4-bis(3-aminopropyl)piperazine linker and a large variety of terminal groups were synthesized. Our aim was to prove that in related bisquinoline, it is the second quinoline moiety that is responsible for cytotoxicity and that it is not an absolute requirement for overcoming resistance to chloroquine (CQ). Eleven compounds displayed a higher selectivity index (ratio CC50/IC50 activity) than CQ, and one of them cured mice infected by Plasmodium berghei. 相似文献
122.
123.
Grellepois F Chorki F Ourévitch M Charneau S Grellier P McIntosh KA Charman WN Pradines B Crousse B Bonnet-Delpon D Bégué JP 《Journal of medicinal chemistry》2004,47(6):1423-1433
New fluoroartemisinin derivatives containing polar or water-soluble functionalities at C-16 (11a-j, 12a-g) were synthesized using the key intermediate 16-bromo-10-trifluoromethyl anhydrodihydroartemisinin 10. The substitution reaction from 10 was more selective than that from the nonfluorinated parent bromide; the allylic bromide 10 underwent no allylic rearrangement and provided only nucleophilic substitution products in high yields with N-, O-, and C-nucleophiles. Among them, amines 11a-c appeared to be highly in vivo efficient antimalarials on mice infected with Plasmodium berghei, more than the reference sodium artesunate 1d. In particular, the most effective piperazinoethanol derivative 11b cured all mice after oral treatment at a dose lower than 10 mg/kg. Further pharmacokinetic studies showed that the bioavailability in rats following oral administration was 25 times greater for 11b than for artemether 1b. 相似文献
124.
Magueur G Crousse B Charneau S Grellier P Bégué JP Bonnet-Delpon D 《Journal of medicinal chemistry》2004,47(10):2694-2699
The synthesis of a series of C-10 trifluoromethyl ethers of artemisinin has been achieved from key bromide 8, itself carried out in two steps from artemisinin. The substitution of 8 with methanol, ethanol, or succinic acid allowed the access of C-10 CF(3) analogues of beta-artemether, beta-arteether, or artesunate, respectively, in good yields (up to 89%). The presence of the CF(3) group at C-10 of artemisinin clearly increased the chemical stability under simulated stomach acid conditions. For example, the CF(3) analogue of arteether was found to be around 45 times more stable than arteether itself. The influence of the CF(3) moiety on biological activity was also highlighted. CF(3) analogues of artemether and arteether exhibited a high in vivo antimalarial activity on mice infected with Plasmodium berghei NK173, with a complete clearance of the parasitemia during the entire observation period (25 days). 相似文献
125.
Ramanandraibe V Grellier P Martin MT Deville A Joyeau R Ramanitrahasimbola D Mouray E Rasoanaivo P Mambu L 《Planta medica》2008,74(4):417-421
Piptadenia pervillei Vatke (Fabaceae) was selected from a screening programme devoted to the search of naturally-occuring antimalarial compounds from plants of Madagascar. Bioassay-guided fractionation of the ethyl acetate extract of the leaves led to the isolation of four phenolic compounds, (+)-catechin ( 1), (+)-catechin 5-gallate ( 2), (+)-catechin 3-gallate ( 3) and ethyl gallate ( 4). Structures were determined by NMR and mass spectroscopy. Compounds 2 and 3 displayed the highest in vitro activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum with IC (50) values of 1.2 microM and 1.0 microM, respectively, and no significant cytotoxicity against the human embryonic lung cells MRC-5 was measured (IC (50) values > 75 microM). Five analogues ( 5 - 9) of (+)-catechin 5-gallate ( 2) were synthesized and evaluated for their antiplasmodial activity. 相似文献
126.
127.
Laurent Mailly Laurence Renaut Sophie Rogée Elodie Grellier Jean-Claude D'Halluin Morvane Colin 《Molecular therapy》2006,14(2):293-304
Gene transfer by adenoviruses, which are widely used for gene therapy, may provide an alternative approach to treatment of several hematopoietic malignancies. However, a major limitation of adenovirus 5-based gene therapy lies in the natural tropism of the virus for the widely expressed hCAR receptor. The efficacy of adenoviral vectors could be improved if viral vectors that exhibit tissue-specific gene delivery were developed. For efficient gene transfer it is essential that every step from binding of virus to target cells to transgene expression is successfully accomplished. We developed a specific vector targeting the CD21 receptor, by inserting a CD21 binding sequence, derived from the EBV GP350/220 protein, into the HI loop of the HAdV5 fiber protein. This vector, HAdV5-CD21HIloop, binds specifically to CD21-positive cells and results in enhanced expression of the transgene in these cells and reduced expression in CD21-negative cells. Viral infection is highly correlated with the presence of CD21 receptors. Taken together, these results demonstrate that HAdV5-CD21HIloop is able to transduce CD21-positive cells specifically with reduced infection of nontarget cells. This is the result of the maintenance of the intracellular trafficking of the genetically modified adenovirus without vesicular retention, leading to enhanced nuclear transfer. 相似文献
128.
Lebrun C Frenay M Lonjon M Marcy PY Grellier P 《La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne》1999,20(3):247-252
INTRODUCTION: The epidemiology of brain or central nervous system metastases is poorly documented. Retrospective studies based on autopsies that were aimed at investigating the incidence and prevalence of brain metastases have revealed the shortfalls in tumour registers. The exact role of cerebral metastases has not been addressed within the scope of cancer considered as a public health issue. CURRENT KNOWLEDGE AND KEY POINTS: The prognosis of brain metastases should not be considered either on general or a priori basis as being poorer than that of other metastatic sites. Evaluation of the role of focal radiation therapy and chemotherapy is still in progress. Appropriate use of therapeutical strategies directed at brain tumors generally improves the condition of most patients. It also usually increases survival and enhances the quality of life. FUTURE PROSPECTS AND PROJECTS: The role of chemotherapy in current therapeutical strategies has not yet been defined and should be investigated and developed. 相似文献
129.
Jean François Grellier Laetitia Vercellino Thierry Leblanc Pascal Merlet Catherine Thieblemont Pierre Weinmann Marie-Elisabeth Toubert Nathalie Berenger Josette Brière Pauline Brice 《European journal of nuclear medicine and molecular imaging》2014,41(11):2023-2030
Purpose
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare Hodgkin lymphoma distinguished from classical Hodgkin lymphoma (cHL) by the nature of the neoplastic cells which express B-cell markers. We wanted to determine the diagnostic performance of FDG PET/CT in initial assessment and its therapeutic impact on staging.Methods
We retrospectively studied a population of 35 patients with NLPHL (8 previously treated for NLHPL, 27 untreated). All patients underwent an initial staging by pretherapeutic FDG PET/CT. The impact on initial stage or relapse stage was assessed by an independent physician.Results
In a per-patient analysis, the sensitivity of the pretherapeutic FDG PET/CT was 100 %. In a per-site analysis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of pretherapeutic FDG PET/CT were 100 %, 99 %, 97 %, 100 % and 99 %, respectively. Pretherapeutic FDG PET/CT led to a change in the initial stage/relapse stage in 12 of the 35 patients (34 %). In contrast to previous results established without FDG PET/CT, 20 % of patient had osteomedullary lesions.Conclusion
Pretherapeutic FDG PET/CT has excellent performance for initial staging or relapse staging of NLPHL. 相似文献130.
Lorena Carneiro Albernaz Gustavo Adolfo Sierra Romero Phillipe Grellier Laila Salmen Espindola 《Journal of ethnopharmacology》2010,131(1):116-630