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排序方式: 共有235条查询结果,搜索用时 15 毫秒
111.
Adi Diab Robert R. Jenq Gabrielle A. Rizzuto Adam D. Cohen Deonka W. Huggins Taha Merghoub Manuel E. Engelhorn José A. Guevara-Pati?o David Suh Vanessa M. Hubbard-Lucey Adam A. Kochman Suzie Chen Hong Zhong Jedd D. Wolchok Marcel R. M. van den Brink Alan N. Houghton Miguel-Angel Perales 《PloS one》2013,8(12)
The development of successful cancer vaccines is contingent on the ability to induce effective and persistent anti-tumor immunity against self-antigens that do not typically elicit immune responses. In this study, we examine the effects of a non-myeloablative dose of total body irradiation on the ability of tumor-naïve mice to respond to DNA vaccines against melanoma. We demonstrate that irradiation followed by lymphocyte infusion results in a dramatic increase in responsiveness to tumor vaccination, with augmentation of T cell responses to tumor antigens and tumor eradication. In irradiated mice, infused CD8+ T cells expand in an environment that is relatively depleted in regulatory T cells, and this correlates with improved CD8+ T cell functionality. We also observe an increase in the frequency of dendritic cells displaying an activated phenotype within lymphoid organs in the first 24 hours after irradiation. Intriguingly, both the relative decrease in regulatory T cells and increase in activated dendritic cells correspond with a brief window of augmented responsiveness to immunization. After this 24 hour window, the numbers of dendritic cells decline, as does the ability of mice to respond to immunizations. When immunizations are initiated within the period of augmented dendritic cell activation, mice develop anti-tumor responses that show increased durability as well as magnitude, and this approach leads to improved survival in experiments with mice bearing established tumors as well as in a spontaneous melanoma model. We conclude that irradiation can produce potent immune adjuvant effects independent of its ability to induce tumor ablation, and that the timing of immunization and lymphocyte infusion in the irradiated host are crucial for generating optimal anti-tumor immunity. Clinical strategies using these approaches must therefore optimize such parameters, as the correct timing of infusion and vaccination may mean the difference between an ineffective treatment and successful tumor eradication. 相似文献
112.
David R. Huggins Chad E. Kruger Kathleen M. Painter David P. Uberuaga 《Bioenergy Research》2014,7(2):598-608
Cereal residues are considered an important feedstock for future biofuel production. Harvesting residues, however, could lead to serious soil degradation and impaired agroecosystem services. Our objective was to evaluate trade-offs of harvesting wheat and barley residues including impacts on soil erosion and quality, soil organic C (SOC), and nutrient removal. We used agricultural data from 369 geo-referenced points on the 37-ha Washington State University Cook Agronomy Farm combined with model simulations to develop straw harvest scenarios for conventional tillage (CT) and no-tillage (NT) and both 2- and 3-year crop rotations with sequences of wheat, barley, and peas. Site-specific estimates of ethanol production from 2- and 3-year rotation scenarios ranged from 681 to 1,541 L ha?1 yr?1, indicating that both crop rotation and site-specific targeting of residue harvest are important factors. Harvesting straw reduced residue C inputs by 46 % and resulted in levels below that required to maintain SOC under CT. This occurred as a function of both straw harvest and low residue producing crops in rotation. Harvesting straw under CT was predicted to reduce soil quality as Soil Conditioning Indices (SCIs) were negative throughout the field. In contrast, SCIs under NT were positive despite straw harvest. Replacement value of nutrients (N, P, K, S) removed in harvested straw averaged $14.54 Mg?1 dry straw and ranged from $36.04 to $80.30 ha?1, while straw harvesting costs averaged $34.25 Mg?1, and the current (2014) market value of straw is $65 Mg?1. We concluded that substantial trade-offs exist in harvesting straw for biofuel, that trade-offs should be evaluated on a site-specific basis, and that support practices such as crop rotation, reduced tillage, and site-specific nutrient management need to be considered if residue harvest is to be sustainable. 相似文献
113.
Due to the limitations of current voltage sensing techniques, optimal filtering of noisy, undersampled voltage signals on
dendritic trees is a key problem in computational cellular neuroscience. These limitations lead to voltage data that is incomplete
(in the sense of only capturing a small portion of the full spatiotemporal signal) and often highly noisy. In this paper we
use a Kalman filtering framework to develop optimal experimental design methods for voltage sampling. Our approach is to use
a simple greedy algorithm with lazy evaluation to minimize the expected square error of the estimated spatiotemporal voltage
signal. We take advantage of some particular features of the dendritic filtering problem to efficiently calculate the Kalman
estimator’s covariance. We test our framework with simulations of real dendritic branching structures and compare the quality
of both time-invariant and time-varying sampling schemes. While the benefit of using the experimental design methods was modest
in the time-invariant case, improvements of 25–100% over more na?ve methods were found when the observation locations were
allowed to change with time. We also present a heuristic approximation to the greedy algorithm that is an order of magnitude
faster while still providing comparable results. 相似文献
114.
Maksym I. Harhun Christopher L. Huggins Kumaran Ratnasingham Durgesh Raje Ray F. Moss Kinga Szewczyk Georgios Vasilikostas Iain A. Greenwood Teck K. Khong Andrew Wan Marcus Reddy 《Journal of cellular and molecular medicine》2012,16(11):2802-2812
Vascular interstitial cells (VICs) are non‐contractile cells with filopodia previously described in healthy blood vessels of rodents and their function remains unknown. The objective of this study was to identify VICs in human arteries and to ascertain their role. VICs were identified in the wall of human gastro‐omental arteries using transmission electron microscopy. Isolated VICs showed ability to form new and elongate existing filopodia and actively change body shape. Most importantly sprouting VICs were also observed in cell dispersal. RT‐PCR performed on separately collected contractile vascular smooth muscle cells (VSMCs) and VICs showed that both cell types expressed the gene for smooth muscle myosin heavy chain (SM‐MHC). Immunofluorescent labelling showed that both VSMCs and VICs had similar fluorescence for SM‐MHC and αSM‐actin, VICs, however, had significantly lower fluorescence for smoothelin, myosin light chain kinase, h‐calponin and SM22α. It was also found that VICs do not have cytoskeleton as rigid as in contractile VSMCs. VICs express number of VSMC‐specific proteins and display features of phenotypically modulated VSMCs with increased migratory abilities. VICs, therefore represent resident phenotypically modulated VSMCs that are present in human arteries under normal physiological conditions. 相似文献
115.
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117.
C Fowler J P Huggins C Hall C J Restall D Chapman 《Biochimica et biophysica acta》1989,980(3):348-356
Highly purified sarcoplasmic reticulum (SR) has been prepared from dog hearts and has been incubated with the triplet probe erythrosinyl isothiocyanate to specifically label the Ca2+-stimulated ATPase (Ca2+-ATPase) of the SR. The rotational mobility of the Ca2+-ATPase has been studied in this erythrosin-labelled SR using time-resolved phosphorescence polarization. Qualitatively, the mobility of the cardiac Ca2+-ATPase resembles that of skeletal muscle SR Ca2+-ATPase. Addition of Ca2+ to SR affects the mobility of the Ca2+-ATPase in a way consistent with a segment of the ATPase altering its orientation relative to the plane of the membrane. Phosphorylation of phospholamban in cardiac SR by the purified catalytic subunit of cAMP-dependent protein kinase, which is known to increase the activity of the Ca2+-ATPase by deinhibition, also alters measured anisotropy. The changes observed are not compatible with dissociation of the Ca2+-ATPase from phospholamban after the latter is phosphorylated. The data are more consistent with phospholamban associating with the Ca2+-ATPase following phosphorylation, or more complex models in which only the hydrophilic domain of phospholamban binds with and dissociates from the Ca2+-ATPase. 相似文献
118.
R Scherer B Graimann J E Huggins S P Levine G Pfurtscheller 《Biomedizinische Technik》2003,48(1-2):31-36
The aim of the present study was to investigate the most significant frequency components in electrocorticogram (ECoG) recordings in order to operate a brain computer interface (BCI). For this purpose the time-frequency ERD/ERS map and the distinction sensitive learning vector quantization (DSLVQ) are applied to ECoG from three subjects, recorded during a self-paced finger movement. The results show that the ERD/ERS pattern found in ECoG generally matches the ERD/ERS pattern found in EEG recordings, but has an increased prevalence of frequency components in the beta range. 相似文献
119.
Martin K Huggins T King C Carroll MA Catapane EJ 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2008,148(2):152-159
We examined effects of manganese on the nervous system and innervation of lateral cilia of Crassostrea virginica. While essential in trace amounts, tissue manganese accumulation is neurotoxic, inducing Manganism, a Parkinson's-like disease in humans. Lateral cilia of the gill of C. virginica are controlled by a reciprocal serotonergic-dopaminergic innervation from their ganglia. Oysters were incubated 3 days in the presence of up to 1 mM manganese, followed by superfusion of the cerebral ganglia, visceral ganglia or gill with dopamine or serotonin. Beating rates of cilia were measured by stroboscopic microscopy of isolated gill preparations or gill preparations with the ipsilateral cerebral and/or visceral ganglia attached. Acute manganese treatments impaired the dopaminergic, cilio-inhibitory system, while having no effect on the serotonergic, cilio-excitatory system, which is in agreement with the proposed mechanism of manganese toxicity in humans. Manganese treatments also decreased endogenous dopamine levels in the cerebral and visceral ganglia, and gills, but not serotonin levels. We demonstrated that manganese disrupts the animal's dopaminergic system, and also that this preparation can be used to investigate mechanisms that underlie manganese neurotoxicity. It also may serve as a model in pharmacological studies of drugs to treat or prevent Manganism and other dopaminergic cell disorders. 相似文献
120.
Huggins J 《Alternatives to laboratory animals : ATLA》2001,29(5):537-546
Words appearing in abstracts of scientific articles are often useful as search terms, particularly those words and word patterns that are unique to the relevant field of endeavour. In view of the heightened interest in obtaining information about alternatives to animal testing, efforts directed toward enhancing retrieval of pertinent references from the biomedical literature are warranted. Words and phrases, and word-phrase co-occurrences describing methods of experimentation in abstracts about alternatives to skin-irritation testing in animals, were evaluated with regard to retrieval efficiency in the National Library of Medicine database, Toxline(. Precision of retrieval was defined as the number of pertinent references found in the total number of citations retrieved. Retrieval precision values ranged from 0.25% to 100%. 相似文献