全文获取类型
收费全文 | 269篇 |
免费 | 14篇 |
出版年
2022年 | 3篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 8篇 |
2014年 | 14篇 |
2013年 | 14篇 |
2012年 | 18篇 |
2011年 | 16篇 |
2010年 | 18篇 |
2009年 | 9篇 |
2008年 | 15篇 |
2007年 | 17篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 10篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 7篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1972年 | 3篇 |
1971年 | 2篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1964年 | 2篇 |
排序方式: 共有283条查询结果,搜索用时 15 毫秒
71.
72.
Gentile G Merlo G Pozzan A Bernasconi G Bax B Bamborough P Bridges A Carter P Neu M Yao G Brough C Cutler G Coffin A Belyanskaya S 《Bioorganic & medicinal chemistry letters》2012,22(5):1989-1994
5-Aryl-4-carboxamide-1,3-oxazoles are a novel, potent and selective series of GSK-3 inhibitors. The optimization of the series to yield compounds with cell activity and brain permeability is described. 相似文献
73.
Sfondrini L Rossini A Besusso D Merlo A Tagliabue E Mènard S Balsari A 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(11):6624-6630
Flagellin, the structural protein subunit of the bacterial flagellum, is specifically recognized by TLR-5 and has potent immunomodulatory effects. The antitumor effects of purified Salmonella typhimurium flagellin were evaluated in mice transplanted s.c. with a weakly immunogenic murine tumor or with its variant stably transfected to express the highly antigenic human HER-2 oncoprotein. Peritumoral administration of flagellin 8-10 days after tumor implantation did not affect the growth rate of the weakly immunogenic tumor but significantly inhibited growth of the antigenic variant tumor. In contrast, flagellin administered at the time of implantation of the antigenic tumor led to accelerated tumor growth. These contrasting effects of flagellin on tumor growth correlated with the type of immune response induced; i.e., late flagellin administration was associated with an increased IFN-gamma:IL-4 ratio and the decreased frequency of CD4+CD25+ T regulatory cells, whereas flagellin treatment at the time of tumor implantation decreased the IFN-gamma:IL-4 ratio and increased CD4+CD25+ T cell frequency. When the early flagellin treatment was combined with administration of CpG-containing oligodeoxynucleotides, tumor growth was completely suppressed, indicating synergy between flagellin and CpG-containing oligodeoxynucleotides. Together, these data provide evidence that flagellin can have contrasting effects on tumor growth. 相似文献
74.
Fiorella Fontana Pasquale Bernardi Carmine Pizzi Santi Spampinato Andrea Bedini Emilio Merlo Pich 《Peptides》2009,30(9):1705-1709
The aim of our study was to evaluate the effects of repeated episodes of angina and induced myocardial ischemia on plasma nociceptin/orphanin FQ (N/OFQ) levels. Patients with unstable angina (23 with new onset severe angina or accelerated angina and 18 with subacute angina at rest) who had had repeated spontaneous episodes of chest pain in the last week before the study underwent myocardial perfusion single-photon emission computed tomography using adenosine infusion. Twenty subjects without clinical symptoms of angina matched for age, sex and cardiac risk factors served as a control group. N/OFQ levels were significantly (P < 0.01) higher in the patients (15.2 ± 2.1 pg/ml) than in the control group (8.5 ± 2.6 pg/ml). Blood pressure and heart rate did not significantly differ. All patients showed transient adenosine infusion myocardial ischemia that did not induce chest pain or significantly modify plasma N/OFQ levels or hemodynamic parameters. Our findings show that unstable angina is associated with a significant increase in circulating N/OFQ levels unrelated to intervening transient myocardial ischemia or hemodynamic changes. This increase is probably related to the chest pain repeatedly occurring in the course of coronary artery disease, but absent during transient adenosine-induced myocardial ischemia. 相似文献
75.
Serdar Korur Roland M. Huber Balasubramanian Sivasankaran Michael Petrich Pier Morin Jr Brian A. Hemmings Adrian Merlo Maria Maddalena Lino 《PloS one》2009,4(10)
Cancers are driven by a population of cells with the stem cell properties of self-renewal and unlimited growth. As a subpopulation within the tumor mass, these cells are believed to constitute a tumor cell reservoir. Pathways controlling the renewal of normal stem cells are deregulated in cancer. The polycomb group gene Bmi1, which is required for neural stem cell self-renewal and also controls anti-oxidant defense in neurons, is upregulated in several cancers, including medulloblastoma. We have found that Bmi1 is consistently and highly expressed in GBM. Downregulation of Bmi1 by shRNAs induced a differentiation phenotype and reduced expression of the stem cell markers Sox2 and Nestin. Interestingly, expression of glycogen synthase kinase 3 beta (GSK3β), which was found to be consistently expressed in primary GBM, also declined. This suggests a functional link between Bmi1 and GSK3β. Interference with GSK3β activity by siRNA, the specific inhibitor SB216763, or lithium chloride (LiCl) induced tumor cell differentiation. In addition, tumor cell apoptosis was enhanced, the formation of neurospheres was impaired, and clonogenicity reduced in a dose-dependent manner. GBM cell lines consist mainly of CD133-negative (CD133-) cells. Interestingly, ex vivo cells from primary tumor biopsies allowed the identification of a CD133- subpopulation of cells that express stem cell markers and are depleted by inactivation of GSK3β. Drugs that inhibit GSK3, including the psychiatric drug LiCl, may deplete the GBM stem cell reservoir independently of CD133 status. 相似文献
76.
Isabella Campanini Andrea Merlo Dario Farina 《Journal of electromyography and kinesiology》2009,19(1):22-29
Motor unit properties were analyzed in patients with upper motor neuron syndrome (UMNS). Multi-channel surface electromyographic (EMG) signals were recorded for 300 s from the biceps brachii muscle of seven male subacute patients (time from lesion, mean ± SE, 4.9 ± 1.0 months). In three patients, both arms were investigated, leading to 10 recorded muscles. Patients were analyzed in rest-like condition with motor units activated due to pathological muscle overactivity. For a total of 12 motor units, the complete discharge pattern was extracted from EMG decomposition. Interpulse interval variability was 7.8 ± 0.9%. At minimum discharge rate (6.4 ± 0.4 pulses per second, pps), conduction velocity was smaller than at maximum discharge rate (12.0 ± 0.9 pps) in all motor units (3.60 ± 0.21 m/s vs. 3.84 ± 0.20 m/s). Conduction velocity changed by 1.35 ± 0.48% (different from zero, P < 0.01) for each increase of 1 pps in discharge rate. It was concluded that conduction velocity of low-threshold motor units in subacute patients with UMNS had similar values as reported in healthy subjects and was positively correlated to instantaneous discharge rate (velocity recovery function of muscle fibers). 相似文献
77.
An optimal protocol for cat semen cryopreservation has not yet been defined. Addition of Equex STM Paste has been tested for epididymal cat spermatozoa but not for ejaculated cat spermatozoa. Furthermore, the effect of Equex STM Paste on fertilizing ability of cryopreserved semen has never been evaluated in that species. Therefore, the aims of the current study were to investigate if addition of Equex STM Paste to a freezing extender for electroejaculated cat (Felis catus) semen would improve postthaw sperm quality and if sperm fertilizing ability after cryopreservation with or without Equex STM Paste was preserved. Semen was collected by electroejaculation and frozen in a Tris-glucose-citrate egg yolk extender supplemented with (0.5% vol/vol) or without Equex STM Paste. In Experiment 1, sperm motility, membrane integrity, and acrosomal status were determined immediately after collection and at 0, 3, and 6 h postthaw. In Experiment 2, frozen semen from the two groups was used for in vitro fertilization (IVF) of in vitro-matured cat oocytes. Cleavage rate was recorded 30 h after IVF, and embryo development was evaluated on Days 6 and 7 of culture. In Experiment 1, the rate of motile spermatozoa after freezing-thawing was higher when Equex STM Paste was added to the freezing extender, but progressive motility score was not influenced (P > 0.05). Sperm membrane integrity was positively affected (P < 0.05) by the addition of the detergent. Intact acrosomes after thawing were similar (P > 0.05) between groups. Even if the decreasing rates of motility and membrane integrity were more rapid in presence of Equex than those in controls, total motility and sperm viability were similar at 3 and 6 h after thawing (P > 0.05). In Experiment 2, there was no difference in fertilizing ability and embryo development between the two groups (P > 0.05). The results of this study demonstrate that the addition of Equex STM Paste in the freezing extender avoids the loss of motile spermatozoa and maintains fertilizing ability of frozen-thawed spermatozoa. 相似文献
78.
María Úbeda-Manzanaro Manuel A. Merlo José L. Palazón Ismael Cross Carmen Sarasquete Laureana Rebordinos 《Genetica》2010,138(7):787-794
In the present study dual-colour fluorescence in situ hybridization (FISH) was performed to study the chromosomal distribution
of 18S and 5S rDNAs, (GATA)n and 5S rDNA, and U2 snRNA and 18S rDNA in four species of Batrachoididae family: Amphichthys cryptocentrus, Batrachoides manglae, Porichthys plectrodon and Thalassophryne maculosa. The 18S rDNA signals were present in only one pair of chromosomes in all the four Batrachoididae species. The 5S rDNA was
mapped on one pair of chromosomes, except in B. manglae, which showed a hybridization signal in two pairs. The two ribosomal genes are located on different chromosome pairs, except
in A. cryptocentrus, in which they appear co-located. In all the cases, the (GATA)n probe produced disperse hybridization signals in all four species. The U2 snRNA signals appear very widely scattered in A. cryptocentrus, P. plectrodon, but show a degree of clustering in a specific chromosome pair in B. manglae. In T.
maculosa, they are thinly dispersed and strong hybridization signals are observed co-located to the 18S rDNA-bearing chromosomes.
Finally, a double-colour FISH with U2 snRNA and 5S rDNA probes was performed in B. manglae, and this showed that these genes were not co-located. These results have been compared with those from another Batrachoididae
species, and evolutive processes of these species are discussed. 相似文献
79.
Discovery and structure–activity relationship of a novel spirocarbamate series of NPY Y5 antagonists
Colin P. Leslie Jonathan Bentley Matteo Biagetti Stefania Contini Romano Di Fabio Daniele Donati Thorsten Genski Sebastien Guery Angelica Mazzali Giancarlo Merlo Domenica A. Pizzi Fabiola Sacco Catia Seri Michela Tessari Laura Zonzini Laura Caberlotto 《Bioorganic & medicinal chemistry letters》2010,20(20):6103-6107
A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5]decan-2-one derivatives was identified with potent NPY Y5 antagonist activity. Optimization of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar Y5 activity with metabolic stability, oral bioavailability, brain penetration and strong preclinical profile for development. Both compounds significantly inhibited the food intake induced by a Y5 selective agonist with minimal effective doses of 3 mg/kg po. 相似文献
80.
KASSO DAÏNOU JEAN‐PHILIPPE BIZOUX JEAN‐LOUIS DOUCET GRÉGORY MAHY OLIVIER J. HARDY MYRIAM HEUERTZ 《Molecular ecology》2010,19(20):4462-4477
The impact of the Pleistocene climate oscillations on the structure of biodiversity in tropical regions remains poorly understood. In this study, the forest refuge theory is examined at the molecular level in Milicia excelsa, a dioecious tree with a continuous range throughout tropical Africa. Eight nuclear microsatellites (nSSRs) and two sequences and one microsatellite from chloroplast DNA (cpDNA) showed a deep divide between samples from Benin and those from Lower Guinea. This suggests that these populations were isolated in separate geographical regions, probably for several glacial cycles of the Pleistocene, and that the nuclear gene pools were not homogenized despite M. excelsa’s wind‐pollination syndrome. The divide could also be related to seed dispersal patterns, which should be largely determined by the migration behaviour of M. excelsa’s main seed disperser, the frugivorous bat Eidolon helvum. Within Lower Guinea, a north–south divide, observed with both marker types despite weak genetic structure (nSSRs: FST = 0.035, cpDNA: GST = 0.506), suggested the existence of separate Pleistocene refugia in Cameroon and the Gabon/Congo region. We inferred a pollen‐to‐seed dispersal distance ratio of c. 1.8, consistent with wide‐ranging gene dispersal by both wind and bats. Simulations in an Approximate Bayesian Computation framework suggested low nSSR and cpDNA mutation rates, but imprecise estimates of other demographic parameters, probably due to a substantial gene flow between the Lower Guinean gene pools. The decline of genetic diversity detected in some Gabonese populations could be a consequence of the relatively recent establishment of a closed canopy forest, which could negatively affect M. excelsa’s reproductive system. 相似文献