全文获取类型
收费全文 | 532篇 |
免费 | 39篇 |
出版年
2023年 | 6篇 |
2022年 | 2篇 |
2021年 | 9篇 |
2020年 | 2篇 |
2019年 | 7篇 |
2018年 | 13篇 |
2017年 | 10篇 |
2016年 | 14篇 |
2015年 | 27篇 |
2014年 | 23篇 |
2013年 | 46篇 |
2012年 | 37篇 |
2011年 | 40篇 |
2010年 | 31篇 |
2009年 | 18篇 |
2008年 | 31篇 |
2007年 | 32篇 |
2006年 | 19篇 |
2005年 | 24篇 |
2004年 | 29篇 |
2003年 | 25篇 |
2002年 | 23篇 |
2001年 | 3篇 |
2000年 | 12篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1940年 | 1篇 |
排序方式: 共有571条查询结果,搜索用时 31 毫秒
1.
Alan Agresti Atalanta Ghosh Matilde Bini 《Biometrical journal. Biometrische Zeitschrift》1995,37(7):811-820
Several authors have noted the dependence of kappa measures of inter-rater agreement on the marginal distributions of contingency tables displaying the joint ratings. This paper introduces a smoothed version of kappa computed after raking the table to achieve pre-specified marginal distributions. A comparison of kappa with raked kappa for various margins can indicate the extent of the dependence on the margins, and can indicate how much of the lack of agreement is due to marginal heterogeneity. 相似文献
2.
Localization of eukaryotic initiation factor 2 in neuron primary cultures and established cell lines
Maria V. T. Lobo F. Javier M. Alonso Susana Rodriguez Alberto Alcazar Elena Martin Francisco Munoz Rafael G-Santander Matilde Salinas Juan L. Fando 《The Histochemical journal》1997,29(6):453-468
Eukaryotic initiation factor 2 (eIF-2) is a heterotrimeric protein with subunits α, β and γ that forms a ternary complex with
Met-tRNA and GTP. It promotes the binding of Met-tRNA to ribosomes and controls translational rates via phosphorylation/dephosphorylation
mechanisms. By means of immunofluorescence and post-embedding immunocytochemistry of intact cells and quantitative immunoblotting
of cell extracts, the cellular distribution of the initiation factor has been examined in primary neuronal cultures as well
as in two established cell lines: PC12 phaeochromocytoma cells and rat pituitary GH4C1 cells. Our results indicated that the
initiation factor is located not only in the cytoplasm but also in the nuclei of the cultured neurons and cell lines. In the
cytoplasm, immunocytochemical studies reveal that the factor is present mainly in those areas that are rich in ribosomes.
In the nucleus, the immunolabelling of eukaryotic initiation factor 2 verified the presence of gold particles in both nucleolar
and extranucleolar areas. The specific distribution of this factor on both sides of the nuclear envelope suggests that it
might have some nuclear-related function(s) besides its already known role in the control of translation 相似文献
3.
Claudia Hernández-Jiménez Rogelio García-Torrentera J. Raúl Olmos-Zú?iga Rogelio Jasso-Victoria Miguel O. Gaxiola-Gaxiola Matilde Baltazares-Lipp Luis H. Gutiérrez-González 《PloS one》2014,9(7)
The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation. 相似文献
4.
5.
Annamaria Tonazzi Cristina Mantovani Matilde Colella Giorgio Terenghi Cesare Indiveri 《Neurochemical research》2013,38(12):2535-2541
The carnitine/acylcarnitine transporter is a transport system whose function is essential for the mitochondrial β-oxidation of fatty acids. Here, the presence of carnitine/acylcarnitine carrier (CACT) in nervous tissue and its sub-cellular localization in dorsal root ganglia (DRG) neurons have been investigated. Western blot analysis using a polyclonal anti-CACT antibody produced in our laboratory revealed the presence of CACT in all the nervous tissue extracts analyzed. Confocal microscopy experiments performed on fixed and permeabilized DRG neurons co-stained with the anti-CACT antibody and the mitochondrial marker MitoTracker Red clearly showed a mitochondrial localization for the carnitine/acylcarnitine transporter. The transport activity of CACT from DRG extracts reconstituted into liposomes was about 50 % in respect to liver extracts. The experimental data here reported represent the first direct evidence of the expression of the carnitine/acylcarnitine transporter in sensory neurons, thus supporting the existence of the β-oxidation pathway in these cells. 相似文献
6.
Feng Luan M. Natália D.S. Cordeiro Nerea Alonso Xerardo García-Mera Olga Caamaño Francisco J. Romero-Duran Matilde Yañez Humberto González-Díaz 《Bioorganic & medicinal chemistry》2013,21(7):1870-1879
The interest on computational techniques for the discovery of neuroprotective drugs has increased due to recent fail of important clinical trials. In fact, there is a huge amount of data accumulated in public databases like CHEMBL with respect to structurally heterogeneous series of drugs, multiple assays, drug targets, and model organisms. However, there are no reports of multi-target or multiplexing Quantitative Structure–Property Relationships (mt-QSAR/mx-QSAR) models of these multiplexing assay outcomes reported in CHEMBL for neurotoxicity/neuroprotective effects of drugs. Accordingly, in this paper we develop the first mx-QSAR model for multiplexing assays of neurotoxicity/neuroprotective effects of drugs. We used the method TOPS-MODE to calculate the structural parameters of drugs. The best model found correctly classified 4393 out of 4915 total cases in both training and validation. This is representative of overall train and validation Accuracy, Sensitivity, and Specificity values near to 90%, 98%, and 80%, respectively. This dataset includes multiplexing assay endpoints of 2217 compounds. Every one compound was assayed in at least one out of 338 assays, which involved 148 molecular or cellular targets and 35 standard type measures in 11 model organisms (including human). The second aim of this work is the exemplification of the use of the new mx-QSAR model with a practical case of study. To this end, we obtained again by organic synthesis and reported, by the first time, experimental assays of the new 1,3-rasagiline derivatives 3 different tests: assay (1) in absence of neurotoxic agents, (2) in the presence of glutamate, and (3) in the presence of H2O2. The higher neuroprotective effects found for each one of these assays were for the stereoisomers of compound 7: compound 7b with protection = 23.4% in assay (1) and protection = 15.2% in assay (2); and for compound 7a with protection = 46.2% in assay (3). Interestingly, almost all compounds show protection values >10% in assay (3) but not in the other 2 assays. After that, we used the mx-QSAR model to predict the more probable response of the new compounds in 559 unique pharmacological tests not carried out experimentally. The results obtained are very significant because they complement the pharmacological studies of these promising rasagiline derivatives. This work paves the way for further developments in the multi-target/multiplexing screening of large libraries of compounds potentially useful in the treatment of neurodegenerative diseases. 相似文献
7.
Andrea Feliciano Josep Castellvi Ana Artero-Castro Jose A. Leal Cleofé Romagosa Javier Hernández-Losa Vicente Peg Angels Fabra Francisco Vidal Hiroshi Kondoh Santiago Ramón y Cajal Matilde E. LLeonart 《PloS one》2013,8(10)
MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3’-UTRs of ENPEP, CK2-α, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-α, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40–56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-α was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-α, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-α, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer. 相似文献
8.
Aldo Scarpa Katarzyna Sikora Matteo Fassan Anna Maria Rachiglio Rocco Cappellesso Davide Antonello Eliana Amato Andrea Mafficini Matilde Lambiase Claudia Esposito Emilio Bria Francesca Simonato Maria Scardoni Giona Turri Marco Chilosi Giampaolo Tortora Ambrogio Fassina Nicola Normanno 《PloS one》2013,8(11)
Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy. 相似文献
9.
Aurelio Ciancio Mariantonietta Colagiero Laura Cristina Rosso Santos Nelida Murga Gutierrez Gaetano Grasso 《Mycoscience》2013,54(5):378-386
A new species of Hirsutella was isolated from unidentified mites on Petri plates inoculated with soil and root fragments collected from asparagus rhizosphere at Virú, Northern Peru. The fungus differs from other Hirsutella species by an envelope surrounding the conidium, conidia dimension and DNA sequences. In PDA cultures, the mycelium produced aerial hyphae with conidiogenous cells mainly at right angles, occasionally showing a secondary conidiophore. The solitary conidia are cymbiform, slightly apiculate, 5.0–6.0 × 3.0–4.0 μm. Phylogenetic analyses with partial rRNA and β-tubulin gene sequences confirmed the fungus as an Hirsutella (Ophiocordycipitaceae). Closest species shown by maximum likelihood and neighbor-joining trees were H. nodulosa and H. aphidis, from which the new species differs for conidium or conidiogenous cells dimensions, lack of synnemata and host type. A recombination event was also detected in the rRNA of the holotype strain, involving Ophiocordyceps sinensis as major parent and O. cochlidiicola as minor parent. A complement, inverted insertion was also found in its rRNA, involving part of the ITS2 and 5.8S regions, flanked by two short nucleotide arrays. Due to conidia dimension and phylogenetic position, the fungus is described as Hirsutella tunicata sp. nov. A review of mononematous Hirsutella species is provided. 相似文献