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131.
Butcher JW Liverton NJ Claremon DA Freidinger RM Jurkiewicz NK Lynch JJ Salata JJ Wang J Dieckhaus CM Slaughter DE Vyas K 《Bioorganic & medicinal chemistry letters》2003,13(6):1165-1168
Novel 5-cyclopropyl-1,4-benzodiazepin-2-ones having various N-l substituents were identified as potent and selective blockers of the slowly activating cardiac delayed rectifier potassium current (I(Ks)). Compound 11 is the most potent I(Ks) channel blocker reported to date. 相似文献
132.
Background
Wide variations in mortality rates persist between different areas in England, despite an overall steady decline. To evaluate a conceptual model that might explain how population and service characteristics influence population mortality variations, an overall null hypothesis was tested: variations in primary healthcare service do not predict variations in mortality at population level, after adjusting for population characteristics.Methodology/Principal Findings
In an observational study of all 152 English primary care trusts (geographical groupings of population and primary care services, total population 52 million), routinely available published data from 2008 and 2009 were modelled using negative binomial regression. Counts for all-cause, coronary heart disease, all cancers, stroke, and chronic obstructive pulmonary disease mortality were analyzed using explanatory variables of relevant population and service-related characteristics, including an age-correction factor. The main predictors of mortality variations were population characteristics, especially age and socio-economic deprivation. For the service characteristics, a 1% increase in the percentage of patients on a primary care hypertension register was associated with decreases in coronary heart disease mortality of 3% (95% CI 1–4%, p = 0.006) and in stroke mortality of 6% (CI 3–9%, p<0.0001); a 1% increase in the percentage of patients recalling being better able to see their preferred doctor was associated with decreases in chronic obstructive pulmonary disease mortality of 0.7% (CI 0.2–2.0%, p = 0.02) and in all cancer mortality of 0.3% (CI 0.1–0.5%, p = 0.009) (continuity of care). The study found no evidence of an association at primary care trust population level between variations in achievement of pay for performance and mortality.Conclusions/Significance
Some primary healthcare service characteristics were also associated with variations in mortality at population level, supporting the conceptual model. Health care system reforms should strengthen these characteristics by delivering cost-effective evidence-based interventions to whole populations, and fostering sustained patient-provider partnerships. 相似文献133.
Udai B. Singh Asha Sahu R.K. Singh Dhananjaya P. Singh Kamlesh K. Meena J.S. Srivastava M.C. Manna 《Biological Control》2012,60(3):262-270
The nematode trapping and mycoparasitic potential of Arthrobotrys oligospora was tested in vitro against Meloidogyne graminicola and Rhizoctonia solani, respectively. Five isolates of A. oligospora were isolated from different locations of India. Diversity of the trapping structures is large and highly dependent on the environmental condition and nature of the fungus. In A. oligospora, a three-dimensional adhesive net (in response to nematode) and hyphal coils developed around the hyphae of R. solani. In vitro trap formation and predacity were tested against second-stage juveniles of M. graminicola (J2) and the interactions between A. oligospora and R. solani were recorded. Under field conditions, we demonstrated the biocontrol potential of A. oligospora against R. solani causing sheath blight of rice (Oryza sativa) for the first time. All the isolates of A. oligospora parasitized and killed M. graminicola and R. solani. Application of A. oligospora, isolate VNS-1, in soil infested with M. graminicola and R. solani reduced the number of root knot by 57.58–62.02%, sheath blight incidence by 55.68–59.32% and lesion length by 54.91–66.66% under green house and miniplot (field) conditions. Applications of A. oligospora to the soil increased plant growth: shoot length by 56.4–68.8%, root length by 44.0–54.55%, fresh weight of shoot and root by 62.91–65.4% and 38.9–44.19%, respectively, as compared to the plants grown in nematode infested soil. 相似文献
134.
Navneet Aujla Keith R. Abrams Melanie J. Davies Nick Taub Timothy C. Skinner Kamlesh Khunti 《PloS one》2009,4(11)
Background
There is a clear relationship between depression and diabetes. However, the directionality of the relationship remains unclear and very little research has considered a multi-ethnic population. The aim of this study was to determine the prevalence of depression in a White-European (WE) and South-Asian (SA) population attending a community diabetes screening programme, and to explore the association of depression with screen-detected Type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR).Methodology/Principal Findings
Participants were recruited from general practices in Leicestershire (United Kingdom) between August 2004 and December 2007. 4682 WE (40–75 years) and 1327 SA participants (25–75 years) underwent an Oral Glucose Tolerance Test, detailed history, anthropometric measurements and completed the World Health Organisation-Five (WHO-5) Wellbeing Index. Depression was defined by a WHO-5 wellbeing score ≤13. Unadjusted prevalence of depression for people in the total sample with T2DM and IGR was 21.3% (21.6% in WE, 20.6% in SA, p = 0.75) and 26.0% (25.3% in WE, 28.9% in SA, p = 0.65) respectively. For people with normal glucose tolerance, the prevalence was 25.1% (24.9% in WE, 26.4% in SA, p = 0.86). Age-adjusted prevalences were higher for females than males. Odds ratios adjusted for age, gender, and ethnicity, showed no significant increase in prevalent depression for people with T2DM (OR = 0.95, 95%CI 0.62 to 1.45) or IGR (OR = 1.17, 95%CI 0.96 to1.42).Conclusions
Prior to the knowledge of diagnosis, depression was not significantly more prevalent in people with screen detected T2DM or IGR. Differences in prevalent depression between WE and SA people were also not identified. In this multi-ethnic population, female gender was significantly associated with depression. 相似文献135.
Uzagare MC Padiya KJ Salunkhe MM Sanghvi YS 《Bioorganic & medicinal chemistry letters》2003,13(20):3537-3540
A new method for the oxidation of nucleoside phosphite triester into phosphate triester under nonbasic and nonaqueous conditions using NBS-DMSO in CH(3)CN has been developed. The utility of this method for solution- and solid-phase synthesis of oligonucleotide is demonstrated. 相似文献
136.
In this study, we report a new approach that allows dissection of distinct pathways regulating induction of early adaptive immunity in response to Mycobacterium tuberculosis (Mtb). We used traceable murine dendritic cells (DCs) and macrophage populations to chart their migratory pattern in response to Mtb, and found that only DCs receiving inflammatory stimuli from Mtb up-regulated their expression of CCR7 and migrated specifically to the draining lymph nodes (LNs). Furthermore, these Mtb-modulated DCs initiated a Th1 response only in the draining LNs. Taken together, these results demonstrate that Mtb-induced modulation of DCs is critical for their migration to regional LNs and ensuing T cell priming. 相似文献
137.
Theoretical mechanism of the formation of cholesteryl chloride from cholesterol and thionyl chloride
This work describes a theoretical approach to the substitution reaction mechanism involving the conversion of cholesterol to cholesteryl chloride. Two chlorosulfite ester molecules were formed as intermediates. An iso-steroid was found as the transition state. The final product was cholesteryl chloride and the side products were HCl and SO2. Calculations were carried out at high level Hartree–Fock theory, using the 6–31G* basis set. From the electronic structure of the reactants, the most important physicochemical properties involved in the reaction pathway were used. Thus, to determine the participation of each molecule and to explain the mechanism of reaction; the total energy, HOMO and LUMO, atomic orbital contribution to frontier orbitals formation, electrostatic potentials, atomic charges, hardness and dipole moment were used. Characterization of intermediates and transition state was supported by their respective energy minima, fundamental frequencies and equilibrium geometry.Figure Synopsis of the reaction pathway. The reaction starts when the lone pair of the Ch oxygen interacts with the sulfur atom, releasing a chloride ion. As a result, the first intermediate is formed. Next, in the first intermediate the nucleophilic chloride ion bonds the electrophilic hydrogen atom, releasing HCl and yielding the second intermediate. In the second intermediate, the electrophilic H-atom from HCl bonds with the lone pair of the Cl atom adjacent to the sulfur atom, restoring HCl. Concurrently, SO2 is liberated and causes the formation of the C3-C5 partial bond and breaking of the C5-C6 -bond leading to the transition state. In the transition state, the electrophilic H from HCl bonds with the Cl lone pair at C6-Cl, forming HCl again and leaving the C6 atom electron-deficient, which restores the C5-C6 -bond and breaks the C3-C5 partial bond. Finally, the electrophilic C3 atom and the nucleophilic Cl atom form a bond, yielding cholesteryl chloride. HCl and SO2 are also formed as side products. The arrows show the rearrangement of electrons. 相似文献
138.
Perturbation of microtubule polymerization by quercetin through tubulin binding: a novel mechanism of its antiproliferative activity 总被引:3,自引:0,他引:3
The dietary flavonoid quercetin has a broad range of biological activities, including potent antitumor activity against several types of tumors. Recently, it has been shown that quercetin inhibits cancer cells proliferation by depleting cellular microtubules and perturbing cellular microtubule functions. However, the direct interactions of quercetin with tubulin and microtubules have not been examined so far. Here, we found that quercetin inhibited polymerization of microtubules and depolymerized microtubules made from purified tubulin in vitro. The binding of quercetin with tubulin was studied using quercetin fluorescence and intrinsic tryptophan fluorescence of tubulin. Quercetin bound to tubulin at a single site with a dissociation constant of 5-7 microM, and it specifically inhibited colchicine binding to tubulin but did not bind at the vinblastine site. In addition, quercetin perturbed the secondary structure of tubulin, and the binding of quercetin stimulated the intrinsic GTPase activity of soluble tubulin. Further, quercetin stabilized tubulin against decay and protected two cysteine residues of tubulin toward chemical modification by 5,5'-dithiobis-2-nitrobenzoic acid. Our data demonstrated that the binding of quercetin to tubulin induces conformational changes in tubulin and a mechanism through which quercetin could perturb microtubule polymerization dynamics has been proposed. The data suggest that quercetin inhibits cancer cells proliferation at least in part by perturbing microtubule functions through tubulin binding. 相似文献
139.
Under strictly non-inductive photoperiods (24-h photoperiods) floral buds were initiated on plants receiving 25 treatments
with Reso (resorcinol) or 8 treatments with GA3 (gibberellic acid) or GA3 + Reso, while water treated control plants did not flower at all. Although a single treatment of plants with GA3 or GA3 + Reso is not adequate to cause induction under LD conditions, its effect is added to the sub-threshold induction caused
by one SD (short day: 8-h photoperiod) cycle. The initiation of floral buds was hastened with an increasing number of SD cycles
accompanying respective number of treatments, the effect of GA3 alone or together with Reso being more pronounced than that of Reso alone. GA3 increased the number of floral buds more than Reso, the number being the highest in plants receiving the respective number
of treatments with the combination GA3 + Reso under both inductive as well as non-inductive photoperiods.
Deceased. 相似文献
140.
Anita Verma Ravi Sharma Durga Prasad Bisen Nameeta Brahme Kamlesh Thakkar Shalinta Tigga Priya Chandrakar 《Luminescence》2023,38(5):576-584
Dy3+-doped CaY2Al4SiO12 phosphors were prepared using the sol–gel method. X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and energy dispersive spectroscopy analyses (EDS) were used to analyse the crystal structure, morphology, and elemental composition of the prepared samples. The luminescence behaviour of the sample was investigated using photoluminescence (PL) and thermoluminescence (TL) techniques. The prepared CaY2Al4SiO12:xDy3+ phosphor showed a characteristic blue and yellow emission at ~480 and 583 nm, respectively, with an excitation wavelength of 350 nm. The most intense PL emission was found for a 4 mol% doping concentration of Dy3+ ions. The CIE diagram of the phosphor showed bluish-white colour emission. For TL studies, the prepared phosphors were irradiated with a 60Co γ (gamma) source and the TL glow curve of the CaY2Al4SiO12:0.04Dy3+ phosphor showed three overlapped peaks. For the Gaussian peaks, Chen's peak shape method was applied to determine the kinetic parameters of the samples. 相似文献