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191.
Historically, probabilistic models for decision support have focused on discrimination, e.g., minimizing the ranking error of predicted outcomes. Unfortunately, these models ignore another important aspect, calibration, which indicates the magnitude of correctness of model predictions. Using discrimination and calibration simultaneously can be helpful for many clinical decisions. We investigated tradeoffs between these goals, and developed a unified maximum-margin method to handle them jointly. Our approach called, Doubly Optimized Calibrated Support Vector Machine (DOC-SVM), concurrently optimizes two loss functions: the ridge regression loss and the hinge loss. Experiments using three breast cancer gene-expression datasets (i.e., , GSE2034, and Chanrion''s datasets) showed that our model generated more calibrated outputs when compared to other state-of-the-art models like Support Vector Machine ( = 0.03, = 0.13, and <0.001) and Logistic Regression ( = 0.006, = 0.008, and <0.001). DOC-SVM also demonstrated better discrimination (i.e., higher AUCs) when compared to Support Vector Machine ( = 0.38, = 0.29, and = 0.047) and Logistic Regression ( = 0.38, = 0.04, and <0.0001). DOC-SVM produced a model that was better calibrated without sacrificing discrimination, and hence may be helpful in clinical decision making. GSE2990相似文献
192.
Finite element aortic injury reconstruction of near side lateral impacts using real world crash data
Belwadi A Siegel JH Singh A Smith JA Yang KH King AI 《Journal of biomechanical engineering》2012,134(1):011006
Traumatic rupture of the aorta (TRA) remains the second most common cause of death associated with motor vehicle crashes, only less prevalent than brain injury. On average, nearly 8000 people die annually in the United States due to blunt injury to the aorta. It is observed that over 80% of occupants who suffer an aortic injury die at the scene due to exsanguination into the chest cavity. In the current study, eight near side lateral impacts, in which TRA occurred, were reconstructed using a combination of real world crash data reported in the Crash Injury Research and Engineering Network (CIREN) database, finite element (FE) models of vehicles, and the Wayne State Human Body Model - II (WSHBM). For the eight CIREN cases reconstructed, the high strain regions in the aorta closely matched with the autopsy data provided. The peak average maximum principal strains in all of the eight CIREN cases were localized in the isthmus region of the aorta, distal to the left subclavian artery, and averaged at 22?±?6.2% while the average maximum pressure in the aorta was found to be 117?±?14.7 kPa. 相似文献
193.
Aditya K Panda Jyoti R Parida Rina Tripathy Sarit S Pattanaik Balachandran Ravindran Bidyut K Das 《Arthritis research & therapy》2012,14(5):R218
Introduction
A role for mannose binding lectin (MBL) in autoimmune diseases has been demonstrated earlier and elevated level of MBL has been shown in systemic lupus erythematosus (SLE) patients. In the current study, we investigated MBL as a potential biomarker for disease activity in SLE.Methods
In a case control study SLE patients (93 females) and 67 age, sex, ethnicity matched healthy controls were enrolled. Plasma MBL levels were quantified by enzyme linked immunosorbent assay (ELISA). Clinical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedures.Results
Plasma MBL levels were significantly high in SLE patients compared to healthy controls (P < 0.0001). MBL levels were variable in different clinical categories of SLE. Lower levels were associated with musculoskeletal and cutaneous manifestations (P = 0.002), while higher and intermediate MBL levels were significantly associated with nephritis in combination with other systemic manifestations (P = 0.01 and P = 0.04 respectively). Plasma MBL correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P = 0.0003, r = 0.36), anti-dsDNA (P < 0.0001, r = 0.54), proteinuria (P < 0.0001, r = 0.42) and negatively correlated with C3 (P = 0.007, r = -0.27) and C4 (P = 0.01, r = -0.29).Conclusions
Plasma MBL is a promising marker in the assessment of SLE disease activity. 相似文献194.
Lanner JT Georgiou DK Dagnino-Acosta A Ainbinder A Cheng Q Joshi AD Chen Z Yarotskyy V Oakes JM Lee CS Monroe TO Santillan A Dong K Goodyear L Ismailov II Rodney GG Dirksen RT Hamilton SL 《Nature medicine》2012,18(2):244-251
Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C). We show here that treatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) prevents this heat-induced sudden death in this mouse model. The protection by AICAR is independent of AMP-activated protein kinase (AMPK) activation and results from a newly identified action of the compound on mutant Ryr1 to reduce Ca(2+) leak from the sarcoplasmic reticulum to the sarcoplasm. AICAR thus prevents Ca(2+)-dependent increases in the amount of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) that act to further increase resting Ca(2+) concentrations. If unchecked, the temperature-driven increases in resting Ca(2+) concentrations and the amounts of ROS and RNS create an amplifying cycle that ultimately triggers sustained muscle contractions, rhabdomyolysis and death. Although antioxidants are effective in reducing this cycle in vitro, only AICAR prevents heat-induced death in vivo. Our findings suggest that AICAR is probably effective in prophylactic treatment of humans with enhanced susceptibility to exercise- and/or heat-induced sudden death associated with RYR1 mutations. 相似文献
195.
We describe here the isolation and characterization of OsiSAP8, a member of stress Associated protein (SAP) gene family from rice characterized by the presence of A20 and AN1 type Zinc
finger domains. OsiSAP8 is a multiple stress inducible gene, induced by various stresses, namely heat, cold, salt, desiccation, submergence, wounding,
heavy metals as well as stress hormone Abscisic acid. OsiSAP8 protein fused to GFP was localized towards the periphery of
the cells in the epidermal cells of infiltrated Nicotiana benthamiana leaves. Yeast two hybrid analysis revealed that A20 and AN1 type zinc-finger domains of OsiSAP8 interact with each other.
Overexpression of the gene in both transgenic tobacco and rice conferred tolerance to salt, drought and cold stress at seed
germination/seedling stage as reflected by percentage of germination and gain in fresh weight after stress recovery. Transgenic
rice plants were tolerant to salt and drought during anthesis stage without any yield penalty as compared to unstressed transgenic
plants.
OsiSAP8 is deposited in the Genbank with the Accession number AY345599. 相似文献
196.
Pseudomonas putida CSV86, a naphthalene-degrading organism, exhibited diauxic growth on aromatic compounds plus glucose, with utilization of aromatics in the first log phase and of glucose in the second log phase. Glucose supplementation did not suppress the activity of degrading enzymes, which were induced upon addition of aromatic compounds. The induction was inhibited by chloramphenicol, suggesting that de novo protein synthesis was essential. Cells showed cometabolism of aromatic compounds and organic acids; however, organic acids suppressed glucose utilization. 相似文献
197.
Jaishankar P Hansell E Zhao DM Doyle PS McKerrow JH Renslo AR 《Bioorganic & medicinal chemistry letters》2008,18(2):624-628
A systematic study of P2 and P3 substitution in a series of vinyl sulfone cysteine protease inhibitors is described. The introduction of a methyl substituent in the P2 phenylalanine aryl ring had a favorable effect on protease inhibition and conferred modest selectivity for rhodesain over cruzain. Rhodesain selectivity could be enhanced further by combining these P2 modifications with certain P3 amide substituents. 相似文献
198.
Pseudomonas putida CSV86 utilizes naphthalene (Nap), salicylate (Sal), benzyl alcohol (Balc), and methylnaphthalene (MN) preferentially over
glucose. Methylnaphthalene is metabolized by ring-hydroxylation as well as side-chain hydroxylation pathway. Although the
degradation property was found to be stable, the frequency of obtaining Nap−Sal−MN−Balc− phenotype increased to 11% in the presence of curing agents. This property was transferred by conjugation to Stenotrophomonas maltophilia CSV89 with a frequency of 7 × 10−8 per donor cells. Transconjugants were Nap+Sal+MN+Balc+ and metabolized MN by ring- as well as side-chain hydroxylation pathway. Transconjugants also showed the preferential utilization
of aromatic compounds over glucose indicating transfer of the preferential degradation property. The transferred properties
were lost completely when transconjugants were grown on glucose or 2YT. Attempts to detect and isolate plasmid DNA from CSV86
and transconjugants were unsuccessful. Transfer of degradation genes and its subsequent loss from the transconjugants was
confirmed by PCR using primers specific for 1,2-dihydroxynaphthalene dioxygenase and catechol 2,3-dioxygenase (C23O) as well
as by DNA–DNA hybridizations using total DNA as template and C23O PCR fragment as a probe. These results indicate the involvement
of a probable conjugative element in the: (i) metabolism of aromatic compounds, (ii) ring- and side-chain hydroxylation pathways
for MN, and (iii) preferential utilization of aromatics over glucose. 相似文献
199.
Mohanty SS Raghavendra K Mittal PK Dash AP 《Journal of industrial microbiology & biotechnology》2008,35(10):1199-1202
Efficacy of culture filtrates of five strains of Metarhizium anisopliae isolated from insects were evaluated against Anopheles stephensi and Culex quinquefasciatus. The culture filtrates released from the strains of M. anisopliae in the YpSs and chitin broths were filtered and used for the bioassays after a growth of 7 days. Among the culture filtrates of five strains, M. anisopliae 892 was found to be more effective against both the mosquitoes. The LC(50) values of culture filtrates of M. anisopliae 892 in chitin broth was lower than the LC(50) of culture filtrates in YpSs broth against first and fourth instars of both the mosquitoes. The LC(50) values of culture filtrates were significantly different between first and fourth instars of A. stephensi (t test; P = 0.0001) and C. quinquefasciatus (t test; P = 0.02). The larvae of A. stephensi were more susceptible than C. quinquefasciatus except in two cases. This is the first report of efficacy of culture filtrates produced by M. anisopliae in chitin broth against mosquitoes and have potential as a biological control agent of mosquitoes. 相似文献
200.
Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence 下载免费PDF全文
Daniel E Neafsey Stephen F Schaffner Sarah K Volkman Daniel Park Philip Montgomery Danny A Milner Jr Amanda Lukens David Rosen Rachel Daniels Nathan Houde Joseph F Cortese Erin Tyndall Casey Gates Nicole Stange-Thomann Ousmane Sarr Daouda Ndiaye Omar Ndir Soulyemane Mboup Marcelo U Ferreira Sandra do Lago Moraes Aditya P Dash Chetan E Chitnis Roger C Wiegand Daniel L Hartl Bruce W Birren Eric S Lander Pardis C Sabeti Dyann F Wirth 《Genome biology》2008,9(12):R171-16