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991.
Valli De Re Laura Caggiari Mariangela De Zorzi Renato Talamini Vito Racanelli Mario D’ Andrea Angela Buonadonna Vittorina Zagonel Erika Cecchin Federico Innocenti Giuseppe Toffoli 《PloS one》2014,9(1)
Objective
To explore genes of the killer-cell immunoglobulin-like receptor (KIR) and of the HLA ligand and their relationship with the outcome of metastatic colorectal cancer (mCRC) patients treated with first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI).Methods
A total of 224 mCRC patients were screened for KIR/HLA typing. The determination of the KIR/HLA combinations was based upon the gene content and variants. Genetic associations with complete response (CR), time to progression (TTP) and overall survival (OS) were evaluated by calculating odds and hazard ratios. Multivariate modeling with prognostic covariates was also performed.Results
For CR, the presence of KIR2DL5A, 2DS5, 2DS1, 3DS1, and KIR3DS1/HLA-Bw4-I80 was associated with increased CR rates, with median ORs ranging from 2.1 to 4.3, while the absence of KIR2DS4 and 3DL1 was associated with increased CR rates (OR 3.1). After univariate analysis, patients that underwent resective surgery of tumor, absence of KIR2DS5, and presence of KIR3DL1/HLA-Bw4-I80 showed a significant better OS (HR 1.5 to 2.8). Multivariate analysis identified as parameters independently related to OS the type of treatment (surgery; HR 2.0) and KIR3DL1/HLA-Bw4-I80 genotype (HR for T-I80 2.7 and for no functional KIR/HLA interaction 1.8). For TTP, no association with KIR/HLA genes was observed.Conclusion
This study, for the first time, evidences that the genotyping for KIR-HLA pairs are found predictive markers associated with complete response and improves overall survival prediction of FOLFIRI treatment response in metastatic colorectal cancer. These results suggest a role of the KIR/HLA system in patient outcome, and guide new research on the immunogenetics of mCRC through mechanistic studies and clinical validation. 相似文献992.
Graziela S. Ceravolo Augusto C. Montezano Maria T. Jord?o Eliana H. Akamine Tiago J. Costa Ana P. Takano Denise C. Fernandes Maria L. Barreto-Chaves Francisco R. Laurindo Rita C. Tostes Zuleica B. Fortes Renato P. Chopard Rhian M. Touyz Maria Helena C. Carvalho 《PloS one》2014,9(11)
The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R) contributes to vascular hypertrophy in angiotensin II (ANG II)–induced hypertension, through a mechanism involving reactive oxygen species (ROS) generation and extracellular signal-regulated kinase (ERK1/2) activation. Male Wistar rats were infused with vehicle (control rats), 400 ng/Kg/min ANG II (ANG II rats) or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg9-Leu8-bradykinin (ANGII+DAL rats), via osmotic mini-pumps (14 days) or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats). After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg) 184±5.9 vs 115±2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE): 21.8±2.7 vs 6.0±1.8] and ERK1/2 phosphorylation (% of control: 218.3±29.4 vs 100±0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17±3.1) and ERK1/2 phosphorylation (137±20.7%) in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC) stimulated with low concentrations (0.1 nM) of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM), B1R antagonist (10 µM) and Tiron (superoxide anion scavenger, 10 mM). These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth. Our findings highlight an important cross-talk between the DABK and ANG II in the vascular system and contribute to a better understanding of the mechanisms involved in vascular remodeling in hypertension. 相似文献
993.
Asma Kassas Ivan C. Moura Yumi Yamashita Jorg Scheffel Claudine Guérin-Marchand Ulrich Blank Peter J. Sims Therese Wiedmer Renato C. Monteiro Juan Rivera Nicolas Charles Marc Benhamou 《PloS one》2014,9(10)
Engagement of high-affinity immunoglobulin E receptors (FcεRI) activates two signaling pathways in mast cells. The Lyn pathway leads to recruitment of Syk and to calcium mobilization whereas the Fyn pathway leads to phosphatidylinositol 3-kinase recruitment. Mapping the connections between both pathways remains an important task to be completed. We previously reported that Phospholipid Scramblase 1 (PLSCR1) is phosphorylated on tyrosine after cross-linking FcεRI on RBL-2H3 rat mast cells, amplifies mast cell degranulation, and is associated with both Lyn and Syk tyrosine kinases. Here, analysis of the pathway leading to PLSCR1 tyrosine phosphorylation reveals that it depends on the FcRγ chain. FcεRI aggregation in Fyn-deficient mouse bone marrow-derived mast cells (BMMC) induced a more robust increase in FcεRI-dependent tyrosine phosphorylation of PLSCR1 compared to wild-type cells, whereas PLSCR1 phosphorylation was abolished in Lyn-deficient BMMC. Lyn association with PLSCR1 was not altered in Fyn-deficient BMMC. PLSCR1 phosphorylation was also dependent on the kinase Syk and significantly, but partially, dependent on detectable calcium mobilization. Thus, the Lyn/Syk/calcium axis promotes PLSCR1 phosphorylation in multiple ways. Conversely, the Fyn-dependent pathway negatively regulates it. This study reveals a complex regulation for PLSCR1 tyrosine phosphorylation in FcεRI-activated mast cells and that PLSCR1 sits at a crossroads between Lyn and Fyn pathways. 相似文献
994.
Renato Pariz Maluta Catherine Mary Logue Monique Ribeiro Tiba Casas Ting Meng Elisabete Aparecida Lopes Guastalli Thaís Cabrera Galv?o Rojas Augusto Cezar Montelli Teruê Sadatsune Marcelo de Carvalho Ramos Lisa Kay Nolan Wanderley Dias da Silveira 《PloS one》2014,9(8)
Avian pathogenic Escherichia coli (APEC) strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic E. coli (ExPEC) strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI) and bacteremia. PCR results showed that genes usually found in the ColV plasmid (tsh, iucA, iss, and hlyF) were associated with APEC strains while fyuA, irp-2, fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII, clpV
Sakai and malX were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian E. coli of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC strains (63.2%) segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC), presented more than 70% of similarity by PFGE. The results demonstrate that some “zoonotic-related” STs (ST117, ST131, ST10CC, ST23CC) are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 E. coli of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential. 相似文献
995.
996.
Tatiane Assone Fernando Vieira de Souza Karen Oliveira Gaester Luiz Augusto Marcondes Fonseca Olinda do Carmo Luiz Fernanda Malta Jo?o Renato Rebello Pinho Fernanda de Toledo Gon?alves Alberto Jose da Silva Duarte Augusto Cesar Penalva de Oliveira Jorge Casseb 《PLoS neglected tropical diseases》2014,8(9)
997.
Previous greenhouse gas (GHG) assessments for the shrub willow biomass crops (SWBC) production system lacked quantitative data on the soil CO2 efflux (Fc). This study quantifies the mean annual cumulative Fc, the C sequestration in the above- and belowground biomass, and the carbon balance of the production system. We utilized four SWBC fields, which have been in production for 5, 12, 14, and 19 years. Two treatments were applied: continuous production (CP)—shrub willows were harvested, and stools were allowed to regrow, and tear-out (TO) (crop removal)—shrub willows were harvested, and stools were sprayed with herbicide following spring, crushed, and mixed into the soil. Mean annual cumulative Fc were measured using dynamic closed chambers (LI-8100A and LI-8150). Across different age classes, the mean cumulative Fc ranged from 27.2 to 35.5 Mg CO2 ha?1 year?1 for CP and 26.5 to 29.3 Mg CO2 ha?1 year?1 for TO. The combined carbon (C) sequestration of the standing above- and belowground biomass, excluding stems, ranged from 50.6 to 94.8 Mg CO2 eqv. ha?1. In the CP treatment, the annual C sequestration in the fine roots and foliage offsets the annual cumulative Fc. Across different age classes, C balances ranged from ?21.5 to ?59.3 Mg CO2 ha?1 for CP and 26.5 to 29.3 Mg CO2 ha?1 for TO. The GHG potential of SWBC is about ?36.3 Mg CO2 eqv. ha?1 at the end of 19 years, suggesting that the SWBC system sequesters C until termination of the crop. 相似文献
998.
Lorenzo Mari Renato Casagrandi Enrico Bertuzzo Andrea Rinaldo Marino Gatto 《Theoretical Ecology》2014,7(4):351-365
The transmission of waterborne pathogens is a complex process that is heavily linked to the spatial characteristics of the underlying environmental matrix as well as to the temporal variability of the relevant hydroclimatological drivers. In this work, we propose a time-varying, spatially explicit network model for the dynamics of waterborne diseases. Applying Floquet theory, which allows to extend results of local stability analysis to periodic dynamical systems, we find conditions for pathogen invasion and establishment in systems characterized by fluctuating environmental forcing, thus extending to time-varying contexts the generalized reproduction numbers recently obtained for spatially explicit epidemiology of waterborne disease. We show that temporal variability may have multifaceted effects on the invasion threshold, as it can either favor pathogen invasion or make it less likely. Moreover, environmental fluctuations characterized by distinctive geographical signatures can produce diversified, highly nontrivial effects on pathogen invasion. Our study is complemented by numerical simulations, which show that pathogen establishment is neither necessary nor sufficient for large epidemic outbreaks to occur in time-varying environments. Finally, we show that our framework can be used to reliably characterize the early geography of epidemic outbreaks triggered by fluctuating environmental conditions. 相似文献
999.
Debora Monteiro Moretti Lalima Gagan Ahuja Rodrigo Dutra Nunes Cecília Oliveira Cudischevitch Carlos Renato Oliveira Daumas-Filho Priscilla Medeiros-Castro Guilherme Ventura-Martins Willy Jablonka Felipe Gazos-Lopes Raquel Senna Marcos Henrique Ferreira Sorgine Klaus Hartfelder Margareth Capurro Georgia Correa Atella Rafael Dias Mesquita Mário Alberto Cardoso Silva-Neto 《PloS one》2014,9(8)