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61.
Immacolata Andolfo Vito A. Lasorsa Francesco Manna Barbara E. Rosato Daniela Formicola Achille Iolascon Mario Capasso 《Journal of cellular and molecular medicine》2020,24(11):6459-6471
Neuroblastoma (NB) is the most common extracranial neoplasm in children. The overall outcome for high-risk NB patients is still unacceptable, therefore, it is critical to deeply understand molecular mechanisms associated with NB, which in turn can be utilized for developing drugs towards the treatment of NB. Protein kinases (TKs) play an essential role in the regulation of cell survival and proliferation. Different kinases, such as anaplastic lymphoma kinase (ALK), Aurora kinase, RET receptor tyrosine kinase, are potential therapeutic targets in various cancers, including NB. We analysed a cohort of 45 high-risk NB patients and 9 NB cell lines by a targeted—(t)NGS custom gene panel (genes codifying for the kinase domains of 90 TKs). We identified somatic variants in four TK genes (ALK, EPHB4, LMTK3 and EPHB6) in NB patients and we functionally characterized an interesting somatic variant, V871I, in EPHB4 gene. EPHB4 plays a crucial role in cardiovascular development and regulates vascularization in cancer-promoting angiogenesis, tumour growth and metastasis. Several EPHB4 mutations have previously been identified in solid and haematological tumour specimens but EPHB4 mutations were not described until now in NB. Interestingly, a re-analysis of public CGH-array showed that the EPHB4 gain is associated with advanced diseases in NB. We further demonstrated that higher EPHB4 expression is correlated to stage 4 of NB and with poor overall survival. Additionally, we also revealed that the EPHB4-V871I accounts for increased proliferation, migration and invasion properties in two NB cell lines by acting on VEGF, c-RAF and CDK4 target genes and by increasing the phosphorylation of ERK1-2 pathway. The use of two EPHB4 inhibitors, JI-101 and NVP-BHG712, was able to rescue the phenotype driven by the variant. Our study suggested that EPHB4 is a promising therapeutic target in high-risk NB. 相似文献
62.
63.
de Niederhäusern S Bondi M Messi P Iseppi R Sabia C Manicardi G Anacarso I 《Current microbiology》2011,62(5):1363-1367
In last decade methicillin-resistant Staphylococcus aureus with high level of vancomycin-resistance (VRSA) have been reported and generally the patients with VRSA infection were also
infected with a vancomycin-resistant Enterococcus (VRE). Considering that the high level of vancomycin-resistance in VRSA isolates seems to involve the horizontal transfer
of Tn1546 transposon containing vanA gene from coinfecting VRE strains, the authors have studied the “in vitro” conjugative transfer of this resistance from VanA
enterococci to S. aureus. Out of 25 matings performed combining five vancomycin-resistant enterococci as donors (three Enterococcus faecalis and two Enterococcus faecium), and five S. aureus as recipients, all clinical isolates, two have been successful using E. faecalis as donor. The transfer of vancomycin-resistance was confirmed by vanA gene amplification in both transconjugants and the resistance was expressed at lower levels (MIC 32 μg/ml) in comparison
with the respective VRE donors (MIC > 128 μg/ml). The vancomycin-resistance of trasconjugants was maintained even after subsequent
overnight passages on MSA plates containing subinhibitory levels of vancomycin. This study shows that the vanA gene transfer can be achieved through techniques “in vitro” without the use of laboratory animals employed, in the only similar
experiment previously carried out by other authors, as substrate for the trasconjugant growth. Moreover, in that previous
experiment, contrary to this study, the vancomycin resistant S. aureus trasconjugants were selected on erythromycin agar and not by direct vancomycin agar selection. 相似文献
64.
Vincenzo Saggiomo Immacolata Santarpia Maria Saggiomo Francesca Margiotta Olga Mangoni 《Polar Biology》2011,34(9):1255-1267
During the late austral summer and early autumn 1995 (March–April), an oceanographic cruise was conducted along the Strait
of Magellan in order to study the photosynthetic performance of phytoplankton assemblages. The high correlations between the
pico–nano fractions and both the total biomass concentrations (Chla) and primary production rates emphasized the role of these fractions in driving the primary production processes. Repeated
P versus E experiments were conducted in the most productive area of the Strait, Paso Ancho, in order to assess the influence of the
tidal currents on phytoplankton photosynthetic performance. These data were compared to those available from a previous cruise
(February–March, 1991) carried out along the Strait. In the Pacific–Andean sector, the primary production processes were highly
controlled by wind, land forcing, and irradiance availability. In the Paso Ancho, the observed highest photosynthetic capacity
P\textm\textB P_{\text{m}}^{\text{B}} (up to 6.5 mgC mgChla
−1 h−1) and the high primary production rates may due to the continuous mixing of the water column forced by the strong tidal currents
within the photic layer. The non-limiting, macro-nutrient concentrations in the Strait indicate that the available irradiance
and the depth of mixed layer are the main driving factors of the primary production processes. The photosynthetic performance
of the phytoplankton assemblages renders the Strait a unique ecosystem, which is more similar to those of the mid-latitudes
than to those of the periantarctic areas. 相似文献
65.
Cocco L Follo MY Faenza I Fiume R Ramazzotti G Weber G Martelli AM Manzoli FA 《Advances in enzyme regulation》2011,51(1):2-12
The existence and function of inositide signaling in the nucleus is well documented and we know that the existence of the inositide cycle inside the nucleus has a biological role. An autonomous lipid-dependent signaling system, independently regulated from its plasma membrane counterpart, acts in the nucleus and modulates cell cycle progression and differentiation.We and others focused on PLCβ1, which is the most extensively investigated PLC isoform in the nuclear compartment. PLCβ1 is a key player in the regulation of nuclear inositol lipid signaling, and, as discussed above, its function could also be involved in nuclear structure because it hydrolyses PtdIns(4,5)P2, a well accepted regulator of chromatin remodelling. The evidence, in a number of patients with myelodysplastic syndromes, that the mono-allelic deletion of PLCβ1 is associated with an increased risk of developing acute myeloid leukemia paves the way for an entirely new field of investigation. Indeed the genetic defect evidenced, in addition to being a useful prognostic tool, also suggests that altered expression of this enzyme could have a role in the pathogenesis of this disease, by causing an imbalance between proliferation and apoptosis. The epigenetics of PLCβ1 expression in MDS has been reviewed as well. 相似文献
66.
67.
Paolo Pelosi Rosa Mastrogiacomo Immacolata Iovinella Elena Tuccori Krishna C. Persaud 《Applied microbiology and biotechnology》2014,98(1):61-70
Odorant-binding proteins (OBPs) are small soluble polypeptides found in sensory organs of vertebrates and insects as well as in secretory glands and are dedicated to detection and release of chemical stimuli. OBPs of vertebrates belong to the family of lipocalin proteins, while those of insects are folded into α-helical domains. Both types of architectures are extremely stable to temperature, organic solvents and proteolytic digestion. These characteristics make OBPs suitable elements for fabricating biosensors to be used in the environment, as well as for other biotechnological applications. The affinity of OBPs for small volatile organic compounds is in the micromolar range, and they have broad specificity to a range of ligands. For biotechnological applications, OBPs can be expressed in bacterial systems at low cost and are easily purified. The large amount of information available on their structures and affinities to different molecules should allow the design of specific mutants with desired characteristics and represent a solid base for tailoring OBPs for different applications. 相似文献
68.
Immacolata Porreca Fulvio D’Angelo Daniela Gentilcore Emanuele Carchia Angela Amoresano Andrea Affuso Michele Ceccarelli Pasquale De Luca Libera Esposito Francesco M Guadagno Massimo Mallardo Antonio Nardone Sergio Maccarone Francesca Pane Marzia Scarfò Paolo Sordino Mario De Felice Concetta Ambrosino 《BMC genomics》2014,15(1)
Background
Comparison of toxicogenomic data facilitates the identification of deregulated gene patterns and maximizes health risk prediction in human.Results
Here, we performed phenotypic anchoring on the effects of acute exposure to low-grade polluted groundwater using mouse and zebrafish. Also, we evaluated two windows of chronic exposure in mouse, starting in utero and at the end of lactation. Bioinformatic analysis of livers microarray data showed that the number of deregulated biofunctions and pathways is higher after acute exposure, compared to the chronic one. It also revealed specific profiles of altered gene expression in all treatments, pointing to stress response/mitochondrial pathways as major players of environmental toxicity. Of note, dysfunction of steroid hormones was also predicted by bioinformatic analysis and verified in both models by traditional approaches, serum estrogens measurement and vitellogenin mRNA determination in mice and zebrafish, respectively.Conclusions
In our report, phenotypic anchoring in two vertebrate model organisms highlights the toxicity of low-grade pollution, with varying susceptibility based on exposure window. The overlay of zebrafish and mice deregulated pathways, more than single genes, is useful in risk identification from chemicals implicated in the observed effects.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1067) contains supplementary material, which is available to authorized users. 相似文献69.
70.
Yu Feng Sun Filomena De Biasio Hui Li Qiao Immacolata Iovinella Shao Xiang Yang Yun Ling Lea Riviello Donatella Battaglia Patrizia Falabella Xin Ling Yang Paolo Pelosi 《PloS one》2012,7(3)