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961.
Viviane E. Bernedo Paredes Hans-Georg Buchholz Martin Gartenschl?ger Markus Breimhorst Mathias Schreckenberger Konrad J. Werhahn 《PloS one》2015,10(11)
Objective
Dopamine is an endogenous neuromodulator in cortical circuits and the basal ganglia. In animal models of temporal lobe epilepsy (TLE), seizure threshold is modulated to some extent by dopamine, with D1-receptors having a pro- and D2-receptors an anticonvulsant effect. We aimed to extend our previously reported results on decreased D2/D3 receptor binding in the lateral epileptogenic temporal lobe and to correlate them with demographic and seizure variables to gain a more comprehensive understanding of the underlying involvement of the dopaminergic system in the epileptogenesis of TLE.Methods
To quantify D2/D3 receptor binding, we studied 21 patients with TLE and hippocampal sclerosis (13 left- and eight right-sided) and 18 controls using PET with the high-affinity dopamine D2/D3-receptor ligand 18F-Fallypride to image striatal and extrastriatal binding. TLE was defined by interictal and ictal video-EEG, MRI and 18F-Fluorodeoxyglucose PET. Voxel-based statistical and regions-of-interest analyses were performed.Results
18F-Fallypride binding potential was significantly reduced in the affected temporal lobe and bilateral putamen. A positive correlation between age at onset of epilepsy and [18F]FP BPnd (binding potential non-displaceable) in temporal regions on the epileptogenic side was found, as well as a negative correlation between epilepsy duration and [18F]FP BPnd in the temporal pole on the epileptogenic side and a positive correlation between the estimated number of lifetime GTCS and [18F]FP BPnd in the hippocampus on the epileptogenic side.Significance
The areas of reduced D2/D3 receptor availability correspond to “the irritative zone” surrounding the epileptogenic area. Moreover, reduced D2/D3 receptor availability was detectable in the basal ganglia, which are suspected to be involved in a control circuit for epileptic seizures. The correlational analysis additionally suggests that increased epilepsy duration leads to increasing impairment of the dopaminergic system. 相似文献962.
Niousha Bolandzadeh Konrad Kording Nicole Salowitz Jennifer C. Davis Liang Hsu Alison Chan Devika Sharma Gunnar Blohm Teresa Liu-Ambrose 《PloS one》2015,10(3)
Introduction
Current research suggests that the neuropathology of dementia—including brain changes leading to memory impairment and cognitive decline—is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies.Methods
We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1–L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation.Results
Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year.Discussion
We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a clinical setting. 相似文献963.
Sandra Wallner-Liebmann Ewa Gralka Leonardo Tenori Manuela Konrad Peter Hofmann Martina Dieber-Rotheneder Paola Turano Claudio Luchinat Kurt Zatloukal 《Genes & nutrition》2015,10(1):1-9
Urine contains a clear individual metabolic signature, although embedded within a large daily variability. Given the potential of metabolomics to monitor disease onset from deviations from the “healthy” metabolic state, we have evaluated the effectiveness of a standardized lifestyle in reducing the “metabolic” noise. Urine was collected from 24 (5 men and 19 women) healthy volunteers over a period of 10 days: phase I, days 1–7 in a real-life situation; phase II, days 8–10 in a standardized diet and day 10 plus exercise program. Data on dietary intake and physical activity have been analyzed by a nation-specific software and monitored by published protocols. Urine samples have been analyzed by 1H NMR followed by multivariate statistics. The individual fingerprint emerged and consolidated with increasing the number of samples and reaches ~100 % cross-validated accuracy for about 40 samples. Diet standardization reduced both the intra-individual and the interindividual variability; the effect was due to a reduction in the dispersion of the concentration values of several metabolites. Under standardized diet, however, the individual phenotype was still clearly visible, indicating that the individual’s signature was a strong feature of the metabolome. Consequently, cohort studies designed to investigate the relation of individual metabolic traits and nutrition require multiple samples from each participant even under highly standardized lifestyle conditions in order to exploit the analytical potential of metabolomics. We have established criteria to facilitate design of urine metabolomic studies aimed at monitoring the effects of drugs, lifestyle, dietary supplements, and for accurate determination of signatures of diseases. 相似文献
964.
Volatiles as Chemosystematic Markers for Distinguishing Closely Related Species within the Pinus mugo Complex 下载免费PDF全文
Konrad Celiński Radosław Bonikowski Aleksandra Wojnicka‐Półtorak Ewa Chudzińska Tomasz Maliński 《化学与生物多样性》2015,12(8):1208-1213
Headspace solid‐phase microextraction (HS‐SPME) coupled to GC/MS analysis was used to identify the constituents of pine‐needle volatiles differentiating three closely‐related pine species within the Pinus mugo complex, i.e., P. uncinata Ramond ex DC., P. uliginosa G.E.Neumann ex Wimm ., and P. mugo Turra . Moreover, chemosystematic markers were proposed for the three analyzed pine species. The major constituents of the pine‐needle volatiles were α‐pinene (28.4%) and bornyl acetate (10.8%) for P. uncinata, δ‐car‐3‐ene (21.5%) and α‐pinene (16.1%) for P. uliginosa, and α‐pinene (20%) and δ‐car‐3‐ene (18.1%) for P. mugo. This study is the first report on the application of the composition of pine‐needle volatiles for the reliable identification of closely‐related pine species within the Pinus mugo complex. 相似文献
965.
966.
Rajeev Malhotra Megan F. Burke Trejeeve Martyn Hannah R. Shakartzi Timothy E. Thayer Caitlin O’Rourke Pingcheng Li Matthias Derwall Ester Spagnolli Starsha A. Kolodziej Konrad Hoeft Claire Mayeur Pawina Jiramongkolchai Ravindra Kumar Emmanuel S. Buys Paul B. Yu Kenneth D. Bloch Donald B. Bloch 《PloS one》2015,10(1)
Objective
Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice.Approach and Results
MGP-deficient mice (MGP-/-) were treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc, beginning one day after birth. Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by staining tissue sections with Alizarin red. Aortic calcification was 80% less in MGP-/- mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control animals (P<0.001 for both). LDN-193189-treated MGP-/- mice survived longer than vehicle-treated MGP-/- mice. Levels of phosphorylated Smad1/5 and Id1 mRNA (markers of BMP signaling) did not differ in the aortas from MGP-/- and wild-type mice. Markers of EndMT and osteogenesis were increased in MGP-/- aortas, an effect that was prevented by LDN-193189. Calcification of isolated VSMCs was also inhibited by LDN-193189.Conclusions
Inhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP-/- mice. The EndMT and osteogenic transdifferentiation associated with MGP deficiency is dependent upon BMP signaling. These results suggest that BMP signal transduction has critical roles in the development of vascular calcification in MGP-deficient mice. 相似文献967.
968.
Gronwald W Brunner K Kirchhöfer R Trenner J Neidig KP Kalbitzer HR 《Journal of biomolecular NMR》2007,37(1):15-30
We present here the computer program AUREMOL-RFAC-3D that is a generalization of the previously published program RFAC for
the fully automated estimation of residual indices (R-factors) from 2D NOESY spectra. It is part of the larger AUREMOL software
package (www.auremol.de). RFAC-3D calculates R-factors directly from two-dimensional homonuclear NOESY spectra as well as
from three-dimensional 15N or 13C edited NOESY-HSQC spectra and thus extends the application range to larger proteins. The fully automated method includes
automated peak picking and integration, a Bayesian noise and artifact recognition and the use of the complete relaxation matrix
formalism. To enhance the reliability of the calculated R-factors the method is also generalized to calculate combined R-factors
from a set of 2D and 3D-spectra. For an optimal combination of the information derived from different sources a plausible
formalism had to be derived. In addition, we present a novel direct R-factors based measure that correlates an R-factors as
defined in this paper to the root mean square deviation of the actual structure from the optimal structure. The new program
has been successfully tested on the histidine containing phosphocarrier protein (HPr) from Staphylococcus carnosus and on the Ras-binding domain (RBD) of the Ral guanine-nucleotide dissociation stimulation factor (RalGDS). 相似文献
969.
Segura-Peña D Lichter J Trani M Konrad M Lavie A Lutz S 《Structure (London, England : 1993)》2007,15(12):1555-1566
The human cytosolic thymidine kinase (TK) and structurally related TKs in prokaryotes play a crucial role in the synthesis and regulation of the cellular thymidine triphosphate pool. We report the crystal structures of the TK homotetramer from Thermotoga maritima in four different states: its apo-form, a binary complex with thymidine, as well as the ternary structures with the two substrates (thymidine/AppNHp) and the reaction products (TMP/ADP). In combination with fluorescence spectroscopy and mutagenesis experiments, our results demonstrate that ATP binding is linked to a substantial reorganization of the enzyme quaternary structure, leading to a transition from a closed, inactive conformation to an open, catalytic state. We hypothesize that these structural changes are relevant to enzyme function in situ as part of the catalytic cycle and serve an important role in regulating enzyme activity by amplifying the effects of feedback inhibitor binding. 相似文献
970.
Get the most out of your metagenome: computational analysis of environmental sequence data 总被引:3,自引:0,他引:3
New advances in sequencing technologies bring random shotgun sequencing of ecosystems within reach of smaller labs, but the complexity of metagenomics data can be overwhelming. Recently, many novel computational tools have been developed to unravel ecosystem properties starting from fragmented sequences. In addition, the so-called 'comparative metagenomics' approaches have allowed the discovery of specific genomic and community adaptations to environmental factors. However, many of the parameters extracted from these data to describe the environment at hand (e.g. genomic features, functional complement, phylogenetic composition) are interdependent and influenced by technical aspects of sample preparation and data treatment, leading to various pitfalls during analysis. To avoid this and complement existing initiatives in data standards, we propose a minimal standard for metagenomics data analysis ('MINIMESS') to be able to take full advantage of the power of comparative metagenomics in understanding microbial life on earth. 相似文献