全文获取类型
收费全文 | 332篇 |
免费 | 29篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 8篇 |
2014年 | 11篇 |
2013年 | 35篇 |
2012年 | 23篇 |
2011年 | 14篇 |
2010年 | 14篇 |
2009年 | 8篇 |
2008年 | 15篇 |
2007年 | 19篇 |
2006年 | 18篇 |
2005年 | 27篇 |
2004年 | 12篇 |
2003年 | 14篇 |
2002年 | 12篇 |
2001年 | 13篇 |
2000年 | 15篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 1篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1970年 | 3篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1964年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有361条查询结果,搜索用时 15 毫秒
111.
Paul A. Sutton Vivian Cody Victor E. Marquez 《Nucleosides, nucleotides & nucleic acids》2013,32(3):613-620
Abstract Crystal structure analyses of 1-(2, 3, 5-tri-0-benzoyl-β-D-ribofuranosyl)-tetrahydro-2H-1, 3-diazepine-2, 4(3H)-dione (I) and 1-(2, 3, 5-tri-0-benzoyl-β-D-ribofuranosyl)-6, 7-dihydro-2H-1, 3-diazepine-2(3H)-one (II) show that the major conformational differences between them lie in the aglycone moiety. In I the aglycone is twisted with C(6) and C(7) above, and C(5) below, the plane of the ring. In II the aglycone has a sofa conformation with C(7) above the plane of the ring. The ribose conformation in both compounds is C(1′)-exo-C(2′)-endo (2T1), the C(4′)-C(5′) orientation is gauche-gauche, and the glycoside linkage is high-anti (X = -104.5(3)° I, -95.2(5)° II, respectively). 相似文献
112.
Pamela L. Russ Lajos Hegedus James A. Kelley Joseph J. Barchi Jr. Victor E. Marquez 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):351-363
Abstract The preferential cis-addition of hydrogen to either face of the carbocyclic double bond of enantiomerically pure cyclopentenyl cytosine (1) was achieved. The resulting saturated carbocyclic nucleosides carbodine (2) and isocarbodine (3) were evaluated against human influenza virus. Carbodine showed the greater potency against this virus but the activity of isocarbodine was still substantial. 相似文献
113.
Joseph J. Barchi Jr Alberto Haces Victor E. Marquez John J. McCormack 《Nucleosides, nucleotides & nucleic acids》2013,32(10):1781-1793
Abstract The 2′-deoxy and ara derivatives of 1-β-(D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) were synthesized by improved routes and tested for their inhibitory properties against cytidine deaminase. It was shown that the Ki′s of both compounds were comparable to that of the parent zebularine in inhibition studies with purified enzyme. In contrast to zebularine, 2′-deoxy and ara zebularine showed only nominal cytotoxicity against MOLT-4 and L1210 cells in vitro. A model compound for the inhibition of deoxycytidylate deaminase, 2′-deoxyzebularine 5′-monophosphate (6), was also prepared. 相似文献
114.
115.
Jose Luis Lopez Concepcion Pérez Catalina Marquez Patricia Cabrera Jose Maria Perez Gema Lucia Ramirez Rafael Ordo?ez Juan Manuel Praena-Fernandez Maria Jose Ortiz 《Reports of Practical Oncology and Radiotherapy》2011,16(5):163-169
Background
Attempts to improve survival outcomes of patients with high risk Ewing''s sarcoma (ES) have focused on chemotherapy dose intensification strategies.Aim
The objective of this study is to retrospectively evaluate clinical characteristics and outcome of pediatric patients with high risk ES treated at a single institution.Materials and methods
From 1995 to 2008, seventeen patients (male:female, 14:3) were treated with dose-intensive therapy in our institution. Median age at diagnosis was 10 years (range: 2–15). Seven patients had metastases at diagnosis (lung in 6 cases and bone in one case). Eleven patients presented with unresectable disease. Fifteen (88.2%) received the Spanish Society of Pediatric Oncology protocol which includes six cycles of vincristine, doxorubicin, ifosfamide and etoposide. Two out of the six cases that were resectable received postoperative radiation. In addition, eleven patients received definitive radiation therapy. Finally, twelve (70.5%) out of 17 patients received myeloablative therapy with melphalan/etoposide. The rest of patients (N = 5) received busulfan/melphalan.Results
Median follow-up was 78 months (range: 15–155 months). Initial responses were complete in all patients, but 9 of them developed progression disease. Seven patients became long-term event-free survivors. No patient died of toxicity after transplantation. The 2- and 5-year overall survival rates for all patients were 93% and 73%, respectively. Event-free survival rates were 74% and 54% at 2 and 5 years, respectively.Conclusion
This single-institution experience suggests that myeloablative therapy against high risk ES is effective and safe. 相似文献116.
Exposure of J774 mouse macrophages to stepwise increasing concentrations of ciprofloxacin, an antibiotic inhibiting bacterial topoisomerases, selects for resistant cells that overexpress the efflux transporter Abcc4 (Marquez et al. [2009] Antimicrob. Agents Chemother. 53: 2410-2416), encoded by the Abcc4 gene located on Chromosome 14qE4. In this study, we report the genomic alterations occurring along the selection process. Abcc4 expression progressively increased upon selection rounds, with exponential changes observed between cells exposed to 150 and 200 μM of ciprofloxacin, accompanied by a commensurate decrease in ciprofloxacin accumulation. Molecular cytogenetics experiments showed that this overexpression is linked to Abcc4 gene overrepresentation, grading from a partial trisomy of Chr 14 at the first step of selection (cells exposed to 100 μM ciprofloxacin), to low-level amplifications (around three copies) of Abcc4 locus on 1 or 2 Chr 14 (cells exposed to 150 μM ciprofloxacin), followed by high-level amplification of Abcc4 as homogeneous staining region (hsr), inserted on 3 different derivative Chromosomes (cells exposed to 200 μM ciprofloxacin). In revertant cells obtained after more than 60 passages of culture without drug, the Abcc4 hsr amplification was lost in approx. 70% of the population. These data suggest that exposing cells to sufficient concentrations of an antibiotic with low affinity for eukaryotic topoisomerases can cause major genomic alterations that may lead to the overexpression of the transporter responsible for its efflux. Gene amplification appears therefore as a mechanism of resistance that can be triggered by non-anticancer agents but contribute to cross-resistance, and is partially and slowly reversible. 相似文献
117.
Movement observation (MO) has been shown to activate the motor cortex of the observer as indicated by an increase of corticomotor excitability for muscles involved in the observed actions. Moreover, behavioral work has strongly suggested that this process occurs in a near-automatic manner. Here we further tested this proposal by applying transcranial magnetic stimulation (TMS) when subjects observed how an actor lifted objects of different weights as a single or a dual task. The secondary task was either an auditory discrimination task (experiment 1) or a visual discrimination task (experiment 2). In experiment 1, we found that corticomotor excitability reflected the force requirements indicated in the observed movies (i.e. higher responses when the actor had to apply higher forces). Interestingly, this effect was found irrespective of whether MO was performed as a single or a dual task. By contrast, no such systematic modulations of corticomotor excitability were observed in experiment 2 when visual distracters were present. We conclude that interference effects might arise when MO is performed while competing visual stimuli are present. However, when a secondary task is situated in a different modality, neural responses are in line with the notion that the observers motor system responds in a near-automatic manner. This suggests that MO is a task with very low cognitive demands which might be a valuable supplement for rehabilitation training, particularly, in the acute phase after the incident or in patients suffering from attention deficits. However, it is important to keep in mind that visual distracters might interfere with the neural response in M1. 相似文献
118.
119.
José Rodrigues Coura Maurício Humberto Pe?a Marquez Jorge Augusto de Oliveira Guerra Patricia Lago Zauza Julio Cesar Miguel José Borges Pereira 《Memórias do Instituto Oswaldo Cruz》2013,108(7):909-913
The serology of human
Trypanosoma cruzi
infection in the Rio Negro microregion is very complex because of the large numbers of false-positive cases that result from low antibody titres and cross-reactions with other infections. In the present study, we collected 4,880 blood samples on filter paper; of these, indirect immunofluorescence (IIF) was strongly reactive in 221 (4.5%), which were considered to be positive (IIF strongly reactive; high intensity of fluorescence) and weakly reactive in 302 (6.2%), which were considered to be doubtful (IIF weakly reactive; low intensity of fluorescence). The confirmatory test on the serum using at least two of three techniques (IIF, conventional ELISA and recombinant ELISA) on 137 samples that were positive in the screening test only confirmed 33 cases (24.1%). Of the 178 samples that were considered doubtful in the screening test, only 10 (5.6%) were considered to be positive in the confirmatory test. Finally, we recommend that the serological diagnosis of
T. cruzi
infection in the Amazon region be made using at least two different techniques, for example immunofluorescence and ELISA and confirmed by Western blot analysis when possible. 相似文献
120.