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261.
Nasim Lowlaavar Charles P. Larson Elias Kumbakumba Guohai Zhou J. Mark Ansermino Joel Singer Niranjan Kissoon Hubert Wong Andrew Ndamira Jerome Kabakyenga Julius Kiwanuka Matthew O. Wiens 《PloS one》2016,11(3)
Background
Pediatric hospital mortality from infectious diseases in resource constrained countries remains unacceptably high. Improved methods of risk-stratification can assist in referral decision making and resource allocation. The purpose of this study was to create prediction models for in-hospital mortality among children admitted with suspected infectious diseases.Methods
This two-site prospective observational study enrolled children between 6 months and 5 years admitted with a proven or suspected infection. Baseline clinical and laboratory variables were collected on enrolled children. The primary outcome was death during admission. Stepwise logistic regression minimizing Akaike’s information criterion was used to identify the most promising multivariate models. The final model was chosen based on parsimony.Results
1307 children were enrolled consecutively, and 65 (5%) of whom died during their admission. Malaria, pneumonia and gastroenteritis were diagnosed in 50%, 31% and 8% of children, respectively. The primary model included an abnormal Blantyre coma scale, HIV and weight-for-age z-score. This model had an area under the curve (AUC) of 0.85 (95% CI, 0.80–0.89) with a sensitivity and specificity of 83% and 76%, respectively. The positive and negative predictive values were 15% and 99%, respectively. Two alternate models with similar performance characteristics were developed withholding HIV and weight-for-age z-score, for use when these variables are not available.Conclusions
Risk stratification of children admitted with infectious diseases can be calculated based on several easily measured variables. Risk stratification at admission can be used for allocation of scarce human and physical resources and to guide referral among children admitted to lower level health facilities. 相似文献262.
263.
David Ehrenberg Niranjan Varma Xavier Deupi Mitsumasa Koyanagi Akihisa Terakita Gebhard F.X. Schertler Joachim Heberle Elena Lesca 《Biophysical journal》2019,116(7):1248-1258
Bistable opsins are photopigments expressed in both invertebrates and vertebrates. These light-sensitive G-protein-coupled receptors undergo a reversible reaction upon illumination. A first photon initiates the cis to trans isomerization of the retinal chromophore—attached to the protein through a protonated Schiff base—and a series of transition states that eventually results in the formation of the thermally stable and active Meta state. Excitation by a second photon reverts this process to recover the original ground state. On the other hand, monostable opsins (e.g., bovine rhodopsin) lose their chromophore during the decay of the Meta II state (i.e., they bleach). Spectroscopic studies on the molecular details of the two-photon cycle in bistable opsins are limited. Here, we describe the successful expression and purification of recombinant rhodopsin-1 from the jumping spider Hasarius adansoni (JSR1). In its natural configuration, spectroscopic characterization of JSR1 is hampered by the similar absorption spectra in the visible spectrum of the inactive and active states. We solved this issue by separating their absorption spectra by replacing the endogenous 11-cis retinal chromophore with the blue-shifted 9-cis JSiR1. With this system, we used time-resolved ultraviolet-visible spectroscopy after pulsed laser excitation to obtain kinetic details of the rise and decay of the photocycle intermediates. We also used resonance Raman spectroscopy to elucidate structural changes of the retinal chromophore upon illumination. Our data clearly indicate that the protonated Schiff base is stable throughout the entire photoreaction. We additionally show that the accompanying conformational changes in the protein are different from those of monostable rhodopsin, as recorded by light-induced FTIR difference spectroscopy. Thus, we envisage JSR1 as becoming a model system for future studies on the reaction mechanisms of bistable opsins, e.g., by time-resolved x-ray crystallography. 相似文献
264.
Vijaya K. Gothwal Seelam Bharani Ramesh Kekunnaya PreetiPatil Chhablani Virender Sachdeva Niranjan K. Pehere Asa Narasaiah Rekha Gunturu 《PloS one》2015,10(5)
PurposeTo evaluate the psychometric properties of the Adult Strabismus-20 (AS-20)- a health-related quality of life (HRQoL) questionnaire in adults with strabismus, and if flawed, to revise the AS-20 and its subscales creating valid measurement scales.Methods584 adults (meanage, 27.5 years) with strabismus were recruited from an outpatient clinic at a South Indian tertiary eye care centre and were administered the AS-20 questionnaire.The AS-20 was translated and back translated into two Indian languages. The AS-20 and its two 10-item subscales – ‘psychosocial’ and ‘function’were assessed separately for fit to the Rasch model, including an assessment of the rating scale, unidimensionality (by principal components analysis), measurement precision by person separation reliability, PSR, targeting, and differential item functioning (DIF; notable > 1.0 logits).ResultsResponse categories were not used as intended, thereby, required re-organization and reducing their number from 5 to 3. The AS-20 had adequate measurement precision (PSR = 0.87) but lacked unidimensionality; however, deletion of the six multi-dimensionality causing items and an additional three misfitting items resulted in 11-item unidimensional questionnaire (AS-11). Two items failed to satisfy the model expectations in the ‘psychosocial’ subscale and were deleted – resulting in an 8-item unidimensional scale with adequate PSR (0.81) and targeting (0.23 logits). One item misfit in the ‘function’ subscale and was deleted—resulting in a 9 item Rasch-revised unidimensional subscale with acceptable PSR (0.80) and targeting (0.97 logits).None of the items displayed notable DIF by age, gender and level of education.ConclusionsThe AS-11 and its two Rasch-revised subscales – 8-item psychosocial and 9-item function subscale may be more appropriate than the original AS-20 and its two 10-item subscales for use as unidimensional measures of HRQoL in adults with strabismus in India. Further work is required to establish the validity of the revised rating scale. 相似文献
265.
Bhavna Gupta B. P. Niranjan Reddy Qi Fan Guiyun Yan Jeeraphat Sirichaisinthop Jetsumon Sattabongkot Ananias A. Escalante Liwang Cui 《PloS one》2015,10(8)
Block II of Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is conserved and has been proposed as a potential candidate for a malaria vaccine. The present study aimed to compare sequence diversity in PvMSP3a block II at a local microgeographic scale in a village as well as from larger geographic regions (countries and worldwide). Blood samples were collected from asymptomatic carriers of P. vivax in a village at the western border of Thailand and PvMSP3α was amplified and sequenced. For population genetic analysis, 237 PvMSP3α block II sequences from eleven P. vivax endemic countries were analyzed. PvMSP3α sequences from 20 village-level samples revealed two length variant types with one type containing a large deletion in block I. In contrast, block II was relatively conserved; especially, some non-synonymous mutations were extensively shared among 11 parasite populations. However, the majority of the low-frequency synonymous variations were population specific. The conserved pattern of nucleotide diversity in block II sequences was probably due to functional/structural constraints, which were further supported by the tests of neutrality. Notably, a small region in block II that encodes a predicted B cell epitope was highly polymorphic and showed signs of balancing selection, signifying that this region might be influenced by the immune selection and may serve as a starting point for designing multi-antigen/stage epitope based vaccines against this parasite. 相似文献
266.
Tejasvi S. Niranjan Cindy Skinner Melanie May Tychele Turner Rebecca Rose Roger Stevenson Charles E. Schwartz Tao Wang 《PloS one》2015,10(2)
X-linked Intellectual Disability (XLID) is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome) in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families) using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders. 相似文献
267.
Matthew O. Wiens Heng Gan Celestine Barigye Guohai Zhou Elias Kumbakumba Jerome Kabakyenga Niranjan Kissoon J. Mark Ansermino Walter Karlen Charles P. Larson Stuart M. MacLeod 《PloS one》2015,10(1)
Background
Children discharged from hospitals in developing countries are at high risk of morbidity and mortality. However, few data describe these outcomes among children seen and discharged from rural outpatient centers.Objective
The objective of this exploratory study was to identify predictors of immediate and follow-up morbidity and mortality among children visiting a rural health center in Uganda.Methods
Subjects 0–12 years of age seeking care with a caregiver were consecutively enrolled from a single rural health center in Southwestern Uganda. Baseline variables were collected by research nurses and outcomes of referral, admission or death were recorded (immediate events). Death, hospital admission and health seeking occurring during the 30 days following the clinic visit were also determined (follow-up events). Univariate logistic regression was performed to identify baseline variables associated with immediate outcome and follow-up outcomes.Results
Over the four-month recruitment period 717 subjects were enrolled. There were 85 (11.9%) immediate events (10.1% were admitted, 2.2% were referred, none died). Forty-seven (7.8%) events occurred within 30 days after the visit (7.3% sought care from a health provider, 1.5% were admitted and 0.5% died). Variables associated with immediate events included living more than 30 minutes from the health center, age older than 5 years, having received an antimalarial prior to the visit, having seen a community health worker prior to the visit, elevated respiratory rate or temperature, and depressed weight-for-age z score or decreased oxygen saturation. These variables were not associated with follow-up events.Conclusions
Sick-child visits at a rural health center in South Western Uganda were associated with rates of mortality and subsequent admission of less than 2% in the period following the sick child visits. Other types of health seeking behavior occurred in approximately 7% of subjects during this same period. Several variables were associated with immediate events but there were no reliable predictors of follow-up events, possibly due to low statistical power. 相似文献268.
B G Niranjan N G Avadhani J DiGiovanni 《Biochemical and biophysical research communications》1985,131(2):935-942
Sonic disrupted mitoplasts from 3-methylcholanthrene (MCA) treated rats can catalyze the formation of benzo(a)pyrene (BaP) adducts with calf thymus DNA in the presence of an NADPH generating system. The mitoplasts used in this study contained less than 1% microsomal marker enzymes: rotenone insensitive NADPH cytochrome c reductase and glucose-6-phosphatase. The rates of BaP metabolism and DNA adduct formation per nanomole cytochrome P-450 were different for MCA induced mitochondrial and microsomal enzymes. The major B(a)P DNA adducts formed in incubations with lysed mitoplasts were derived from reaction of 9-OH-B(a)P-4,5 oxide with deoxyguanosine. The results suggest a potential role of mitochondrial monooxygenase activity in the covalent binding of B(a)P to mitochondrial DNA. 相似文献
269.
Niranjan M. Kumar S. L. Sigurdson D. Sheppard Jamson S. Lwebuga-Mukasa 《Experimental cell research》1995,221(2)
The transforming growth factors-β (TGFs-β) family of genes plays important roles in cell growth and differentiation in many cell types. TGFβ modulates the synthesis and accumulation of extracellular matrix (ECM) components and the expression of cell surface receptors for ECM components. TGFβ is increased in alveolar lining fluid during inflammatory reactions of the lung and has been identified in alveolar epithelial cells of developing lungs and hyperplastic type II cells during repair. However, little is known about how TGFβ may regulate expression of extracellular matrix proteins and ECM receptors in lung alveolar epithelial cells. Laminin, a major glycoprotein component of epithelial basement membrane, is synthesized and secreted by alveolar epithelial cells. To study the effects of TGFβ on modulation of laminin and its integrin receptors α6β1 and α3β1 in lung alveolar epithelial cells, a rat alveolar type II cell-derived cell line, LM5, was incubated with TGFβ1 (0-100 pg/ml) in serum-free medium for 0-16 h. We examined the expression of integrin subunits and laminin β2 chain (s-laminin) mRNAs and protein expression. By Northern blot analysis, TGFβ1 induced dose-dependent increases in α6 and β1 mRNA levels. TGFβ1 also increased the expression of laminin β2 chain mRNA at 12-16 h poststimulation. In contrast, TGFβ decreased α3 mRNA expression. Immunoprecipitation studies of TGFβ1-treated cells showed increased surface expression of both α6 and β1 protein while surface expression of the α3 integrin subunit was decreased. The same treatment resulted in increased laminin protein expression. These data suggest that TGFβ1 may regulate alveolar epithelial cell differentiation in part through its modulation of integrins and laminin chains. 相似文献
270.
Short oligopeptides (14 residues) derived from the DNA recognition helix of the phage 434 repressor (434R) have been tethered
onto the metallointercalating [Rh(phi)2(phen′)]3+, and the DNA recognition characteristics of the resultant metal-peptide complexes have been examined. DNA sequence selectivities
for the family of metal-peptide complexes, determined in photoactivated DNA cleavage experiments, reproduce features of operator
recognition by the native 434R. Binding to the DNA duplex depends both on the appended peptide and upon the metallointercalating
unit, as determined through variations in the peptide sequence and in the diastereomeric configuration of the metal-peptide.
The complexes preferentially target 5′-ACAA-3′ operator sites and single-base variants, bind at 50 nM concentrations, and,
as determined by chemical footprinting, protect 7–10 bp of DNA around the target sites. Comparative cleavage studies on synthetic
oligonucleotides containing variations in operator sequence, furthermore, reveal a hierarchy in sequence preference which
resembles the native protein, but highest affinity for the metal-peptides, unlike 434R, is found for 5′-ACGA-3′. These studies
illustrate a new route to the rational design of small, artificial repressors through the construction of metal-peptide complexes.
Received: 18 June 1997 / Accepted: 11 September 1997 相似文献