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51.
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Background:
Metformin is widely accepted as first-line pharmacotherapy for patients with type 2 diabetes mellitus when glycemic control cannot be achieved by lifestyle interventions alone. However, uncertainty exists regarding the optimal second-line therapy for patients whose diabetes is inadequately controlled by metformin monotherapy. Increased use of newer, more costly agents, along with the rising incidence of type 2 diabetes, carries significant budgetary implications for health care systems. We conducted this analysis to determine the relative costs, benefits and cost-effectiveness of options for second-line treatment of type 2 diabetes.Methods:
We used the United Kingdom Prospective Diabetes Study Outcomes Model to forecast diabetes-related complications, quality-adjusted life-years and costs of alternative second-line therapies available in Canada for adults with type 2 diabetes inadequately controlled by metformin. We obtained clinical data from a systematic review and mixed treatment comparison meta-analysis, and we obtained information on costs and utilities from published sources. We performed extensive sensitivity analyses to test the robustness of results to variation in inputs and assumptions.Results:
Sulphonylureas, when added to metformin, were associated with the most favourable cost-effectiveness estimate, with an incremental cost of $12 757 per quality-adjusted life-year gained, relative to continued metformin monotherapy. Treatment with other agents, including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had unfavourable cost-effectiveness estimates compared with sulphonylureas. These results were robust to extensive sensitivity analyses.Interpretation:
For most patients with type 2 diabetes that is inadequately controlled with metformin monotherapy, the addition of a sulphonylurea represents the most cost-effective second-line therapy.Type 2 diabetes mellitus is a progressive disease typically treated in a stepwise fashion, beginning with lifestyle modification, followed by the addition of one or more oral antihyperglycemic drugs and, finally, administration of exogenous insulin. Metformin monotherapy is widely recommended as first-line pharmacotherapy,1,2 given its favourable effects in controlling blood glucose and body weight, low risk of hypoglycemia, low cost and association with mortality benefit.3 Multiple second-line treatment strategies are available for patients in whom glycemic control has become inadequate. These approaches are typically used in addition to continued metformin therapy.4,5 Numerous second-line agents are available in Canada, including older oral agents, such as sulphonylureas, and more recently introduced agents, such as thiazolidinediones and dipeptidyl peptidase-4 inhibitors.The large number of choices for second-line therapy has increased uncertainty regarding the optimal treatment pathway. Recent clinical practice guidelines, including those produced by the Canadian Diabetes Association1 and by the American Diabetes Association and the European Association for the Study of Diabetes,2 have suggested selecting from among several agents on the basis of their respective advantages and disadvantages. There has been a considerable increase in the use of newer, more costly oral antihyperglycemic agents, which has resulted in substantial increases in associated costs to patients and both public and private drug plans in Canada.4 In light of current therapeutic uncertainty, the large proportion of patients requiring second-line therapy over time3,6 and the increasing prevalence of type 2 diabetes,7 the utilization and cost of second-line therapy are likely to continue to grow.Informed decisions regarding optimal prescribing and reimbursement of second-line agents by public and private health care payers requires information about clinical benefits, costs and cost-effectiveness.8 As part of a larger initiative to determine optimal prescribing of antihyperglycemic agents, we sought to determine the incremental cost-effectiveness of treatment with alternative second-line agents added to metformin in patients with type 2 diabetes no longer adequately controlled by metformin monotherapy. 相似文献54.
Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture.
DD commonly occurs in individuals of northern European extraction. Cellular components and processes associated with DD pathogenesis
include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components.
Histology has shown increased but varying levels of particular types of collagen, myofibroblasts and myoglobin proteins in
DD tissue. Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. Although the
existing available biological information on DD may contain potentially valuable (though largely uninterpreted) information,
the precise aetiology of DD remains unknown. Systems biology combines mechanistic modelling with quantitative experimentation
in studies of networks and better understanding of the interaction of multiple components in disease processes. Adopting systems
biology may be the ideal approach for future research in order to improve understanding of complex diseases of multifactorial
origin. In this review, we propose that DD is a disease of several networks rather than of a single gene, and show that this
accounts for the experimental observations obtained to date from a variety of sources. We outline how DD may be investigated
more effectively by employing a systems biology approach that considers the disease network as a whole rather than focusing
on any specific single molecule. 相似文献
55.
Anwar J Shafique U Waheed-uz-Zaman un Nisa Z Munawar MA Jamil N Salman M Dar A Rehman R Saif J Gul H Iqbal T 《International journal of phytoremediation》2011,13(5):410-420
Adsorption is an environmental friendly process for removal and/or recovery of heavy metals from wastewater. In recent years, it has been substantiated as a popular technique to treat industrial waste effluents, with significant advantages. In this work, batchwise removal of chromium (III) ions from water by Polyalthia longifolia leaves was studied as a function of adsorbent dose, pH, contact time, and agitation speed. Surface characteristics of the leaves were evaluated by recording IR spectra. The Langmuir, Freundlich, and Temkin adsorption isotherms were employed to explain the sorption process. It was found that one gram of leaves can remove 1.87 mg of trivalent chromium when working at pH 3.0. It has been concluded that Polyalthia longifolia leaves can be used as cost-effective and benign adsorbents for removal of Cr(III) ions from wastewater. 相似文献
56.
Gandhi HT Vales MI Watson CJ Mallory-Smith CA Mori N Rehman M Zemetra RS Riera-Lizarazu O 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(3):561-572
Aegilops cylindrica Host (2n=4x=28, genome CCDD) is an allotetraploid formed by hybridization between the diploid species Ae. tauschii Coss. (2n=2x=14, genome DD) and Ae. markgrafii (Greuter) Hammer (2n=2x=14, genome CC). Previous research has shown that Ae. tauschii contributed its cytoplasm to Ae. cylindrica. However, our analysis with chloroplast microsatellite markers showed that 1 of the 36 Ae. cylindrica accessions studied, TK 116 (PI 486249), had a plastome derived from Ae. markgrafii rather than Ae. tauschii. Thus, Ae. markgrafii has also contributed its cytoplasm to Ae. cylindrica. Our analysis of chloroplast and nuclear microsatellite markers also suggests that D-type plastome and the D genome in Ae. cylindrica were closely related to, and were probably derived from, the tauschii gene pool of Ae. tauschii. A determination of the likely source of the C genome and the C-type plastome in Ae. cylindrica was not possible. 相似文献
57.
58.
The preference for foraging in groups and the effect of physiognomic factors of a habitat on its use by foraging Whinchats
(Saxicola rubetra) was studied during spring migration stopover in a mosaic cultural landscape at the SE Adriatic coast. Every record of spatially
distinct Whinchats, either a solitary individual or a group, was referred to as a Whinchat unit. The units were classified
as intensively foraging, less intensively foraging or non-foraging and divided into four size classes. The effect of physiognomic
habitat factors on use of habitat by foraging Whinchat units was modelled. All possible additive models using logit link function
were constructed from five independent physiognomic variables: (1) natural perches (NP), (2) artificial perches (AP), (3)
high herbal vegetation (HHV), (4) open bushes (OB) and (5) heterogeneity of vegetation types (HVT). Variables HHV and OB were
included simultaneously in the models. Models that were substantially supported by the data were selected according to second
order Akaike’s information criterion AICc. Two such models contained variable(s) (1) NP and (2) NP + AP. The relative importance weights of physiognomic variables
NP, AP, HVT, HHV and OB were 1, 0.38, 0.24, 0.13 and 0.13, respectively. Perches were thus the most important physiognomic
habitat factor affecting habitat use by Whinchats in a mosaic cultural landscape. The great majority of Whinchats foraged
in groups and the proportion of intensively foraging Whinchat units increased with unit size, leading to the conclusion that
Whinchats preferred social to solitary foraging on the spring stopover at the SE Adriatic coast. 相似文献
59.
Uricase from bovine kidney, purified to homogeneity level, had a molecular weight of 70 kDa. The apparent K(m) and V(max) values for uric acid hydrolysis were 0.125 mM and 102 IU mg(-1) protein respectively. The activation energy requirement for uric acid hydrolysis by uricase and inactivation of enzyme were 11.6 and 14.5 kJ/M respectively. Both enthalpy (Delta H*) and entropy of activation (Delta S*) for uricase activity were lower than those reported for some thermostable enzymes. 相似文献
60.
Raza ZA Khan MS Khalid ZM Rehman A 《Zeitschrift für Naturforschung. C, Journal of biosciences》2006,61(1-2):87-94
The present investigation dealt with the use of previously isolated and studied gamma-ray mutant strain Pseudomonas aeruginosa EBN-8 for the production of biosurfactant by using different hydrocarbon substrates viz. n-hexadecane, paraffin oil and kerosene oil, provided in minimal medium, as the sole carbon and energy sources. The batch experiments were conducted in 250 mL Erlenmeyer flasks, containing 50 mL minimal salt media supplemented with 1% (w/v) hydrocarbon substrate, inoculated by EBN-8 and incubated at 37 degrees C and 100 rpm in an orbital shaker. The sampling was done on 24 h basis for 10 d. The surface tension of cell-free culture broth decreased from 53 to 29 mN/m after 3 and 4 d of incubation when the carbon sources were paraffin oil and n-hexadecane, respectively. The largest reduction in interfacial tension from 26 to 0.4 mN/m was observed with n-hexadecane, while critical micelle dilution was obtained as 50 x CMC for paraffin oil as carbon source. When grown on n-hexadecane and paraffin oil, the EBN-8 mutant strain gave 4.1 and 6.3 g of the rhamnolipids/L, respectively. These surface-active substances subsequently allowed the hydrocarbon substrates to disperse readily as emulsion in aqueous phase. 相似文献