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51.
The linear, positive-stranded RNA genome of flaviviruses is thought to adopt a circularized conformation via interactions of short complementary sequence elements located within its terminal regions. This process of RNA cyclization is a crucial precondition for RNA replication. In the case of mosquito-borne flaviviruses, highly conserved cyclization sequences (CS) have been identified, and their functionality has been experimentally confirmed. Here, we provide an experimental identification of CS elements of tick-borne encephalitis virus (TBEV). These elements, termed 5'-CS-A and 3'-CS-A, are conserved among various tick-borne flaviviruses, but they are unrelated to the mosquito-borne CS elements and are located at different genomic positions. The 5'-CS-A element is situated upstream rather than downstream of the AUG start codon and, in contrast to mosquito-borne flaviviruses, it was found that the entire protein C coding region is not essential for TBEV replication. The complementary 3'-CS-A element is located within the bottom stem rather than upstream of the characteristic 3'-terminal stem-loop structure, implying that this part of the proposed structure cannot be formed when the genome is in its circularized conformation. Finally, we demonstrate that the CS-A elements can also mediate their function when the 5'-CS-A element is moved from its natural position to one corresponding to the mosquito-borne CS. The recognition of essential RNA elements and their differences between mosquito-borne and tick-borne flaviviruses has practical implications for the design of replicons in vaccine and vector development. 相似文献
52.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease selectively affecting upper and lower motor neurons. Patients with ALS suffer from progressive paralysis and eventually die on average after three years. The underlying neurobiology of upper motor neuron degeneration and its effects on the complex network of the brain are, however, largely unknown. Here, we examined the effects of ALS on the structural brain network topology in 35 patients with ALS and 19 healthy controls. Using diffusion tensor imaging (DTI), the brain network was reconstructed for each individual participant. The connectivity of this reconstructed brain network was compared between patients and controls using complexity theory without - a priori selected - regions of interest. Patients with ALS showed an impaired sub-network of regions with reduced white matter connectivity (p = 0.0108, permutation testing). This impaired sub-network was strongly centered around primary motor regions (bilateral precentral gyrus and right paracentral lobule), including secondary motor regions (bilateral caudal middle frontal gyrus and pallidum) as well as high-order hub regions (right posterior cingulate and precuneus). In addition, we found a significant reduction in overall efficiency (p = 0.0095) and clustering (p = 0.0415). From our findings, we conclude that upper motor neuron degeneration in ALS affects both primary motor connections as well as secondary motor connections, together composing an impaired sub-network. The degenerative process in ALS was found to be widespread, but interlinked and targeted to the motor connectome. 相似文献
53.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
54.
van Osch GJ Mandl EW Marijnissen WJ van der Veen SW Verwoerd-Verhoef HL Verhaar JA 《Biorheology》2002,39(1-2):215-220
Tissue engineering of cartilage consists of two steps. Firstly, the cells from a small biopsy of patient's own tissue have to be multiplied. During this multiplication process they lose their cartilage phenotype. In the second step, these cells have to be stimulated to re-express their cartilage phenotype and produce cartilage matrix. Growth factors can be used to improve cell multiplication, redifferentiation and production of matrix. The choice of growth factors should be made for each phase of the tissue engineering process separately, taking into account cell phenotype and the presence of extracellular matrix. This paper demonstrates some examples of the use of growth factors to increase the amount, the quality and the assembly of the matrix components produced for cartilage tissue engineering. In addition it shows that the "culture history" (e.g., addition of growth factors during cell multiplication or preculture period in a 3-dimensional environment) of the cells influences the effect of growth factor addition. The data demonstrate the potency as well as the limitations of the use of growth factors in cartilage tissue engineering. 相似文献
55.
Microorganisms are associated with a variety of ancient geological materials. However, conclusive proof that these organisms
are as old as the geological material and not more recent introductions has generally been lacking. Over the years, numerous
reports of the isolation of ancient bacteria from geological materials have appeared. Most of these have suffered from the
fact that the protocol for the surface sterilization of the sample was either poorly defined, inadequate or rarely included
data to validate the overall effectiveness of the sterilization protocol. With proper sterility validation and isolation protocol,
a legitimate claim for the isolation of an ancient microbe can be made. Biochemical, physiological, or morphological data
indicate that these ancient microbes are not significantly different from modern isolates. As the role (decomposition) of
modern and ancient microbes has not changed over time, it is probably unreasonable to expect these organisms to be vastly
different. A discussion on the reasons for the homogeneity of ancient and modern microbes is presented. Journal of Industrial Microbiology & Biotechnology (2002) 28, 32–41 DOI: 10.1038/sj/jim/7000174
Received 20 May 2001/ Accepted in revised form 16 June 2001 相似文献
56.
Previously we have demonstrated the presence of presynaptic nicotinic acetylcholine receptors on the terminals of myenteric neurons in Auerbach's plexus of guinea-pig ileum. During these studies we observed, that the presence of hemicholinium-3, an inhibitor of the high affinity choline uptake significantly influences the contraction of the longitudinal muscle strip preparation. Our aim was to investigate the neurochemical background of this effect and quantitatively characterize the action of HC-3. We studied the effect of HC-3 on epibatidine- and electrical stimulation-evoked contraction and release of [3H]acetylcholine from the guinea-pig longitudinal muscle strip preparation. We found that in the presence of tetrodotoxin, when the contribution of somatodendritic nicotinic acetylcholine receptors to the response was prevented due to the inhibition of axonal conduction, HC-3 inhibited the epibatidine-evoked contraction and [3H]acetylcholine release in the submicromolar range (IC50 = 897 nM and IC50 = 693 nM, respectively), whereas the electrical stimulation-evoked contraction was not affected by HC-3, and the release of [3H]acetylcholine was apparently enhanced. Our data indicate that HC-3 inhibits the presynaptic nicotinic acetylcholine receptors of myenteric neurons. Since these receptors play an important role in the regulation of cholinergic neurotransmission in the enteric nervous system, the use of HC-3 in [3H]acetylcholine release experiments might bias the interpretation of data. 相似文献
57.
Architecture of epigenetic reprogramming following Twist1-mediated epithelial-mesenchymal transition
Gabriel G Malouf Joseph H Taube Yue Lu Tapasree Roysarkar Shoghag Panjarian Marcos RH Estecio Jaroslav Jelinek Jumpei Yamazaki Noel J-M Raynal Hai Long Tomomitsu Tahara Agata Tinnirello Priyanka Ramachandran Xiu-Ying Zhang Shoudan Liang Sendurai A Mani Jean-Pierre J Issa 《Genome biology》2013,14(12):R144
58.
10 mM D-galactosamine enhibited protein synthesis (1 h incubation time) by 67% in isolated mouse liver cells. Counteracting uridylate deficiency induced by D-galactosamine by preventive administration of 20 mM uridine did not decrease the extent of protein synthesis inhibition. 20 mM D-galactose reverted the inhibition of protein synthesis by D-galactosamine. 10(-5) M epinephrine and 10(-7) M glucagon decreased the incorporation of D-galactosamine into glycogen to 38% and 26% of the control value, respectively, after a 35 min incubation and reduced the inhibition of protein synthesis by D-galactosamine effectively. Experimental evidence supports the view that aminoglycogen formed after D-galactosamine treatment is responsible for the inhibition of protein synthesis. 相似文献
59.
Andrew J. Zimolzak Claire M. Spettell Joaquim Fernandes Vincent A. Fusaro Nathan P. Palmer Suchi Saria Isaac S. Kohane Magdalena A. Jonikas Kenneth D. Mandl 《PloS one》2013,8(11)
Background
Medication nonadherence costs $300 billion annually in the US. Medicare Advantage plans have a financial incentive to increase medication adherence among members because the Centers for Medicare and Medicaid Services (CMS) now awards substantive bonus payments to such plans, based in part on population adherence to chronic medications. We sought to build an individualized surveillance model that detects early which beneficiaries will fall below the CMS adherence threshold.Methods
This was a retrospective study of over 210,000 beneficiaries initiating statins, in a database of private insurance claims, from 2008-2011. A logistic regression model was constructed to use statin adherence from initiation to day 90 to predict beneficiaries who would not meet the CMS measure of proportion of days covered 0.8 or above, from day 91 to 365. The model controlled for 15 additional characteristics. In a sensitivity analysis, we varied the number of days of adherence data used for prediction.Results
Lower adherence in the first 90 days was the strongest predictor of one-year nonadherence, with an odds ratio of 25.0 (95% confidence interval 23.7-26.5) for poor adherence at one year. The model had an area under the receiver operating characteristic curve of 0.80. Sensitivity analysis revealed that predictions of comparable accuracy could be made only 40 days after statin initiation. When members with 30-day supplies for their first statin fill had predictions made at 40 days, and members with 90-day supplies for their first fill had predictions made at 100 days, poor adherence could be predicted with 86% positive predictive value.Conclusions
To preserve their Medicare Star ratings, plan managers should identify or develop effective programs to improve adherence. An individualized surveillance approach can be used to target members who would most benefit, recognizing the tradeoff between improved model performance over time and the advantage of earlier detection. 相似文献60.
Csala M Senesi S Bánhegyi G Mandl J Benedetti A 《Archives of biochemistry and biophysics》2005,440(2):173-180
The transport of sulfate ion across the endoplasmic reticulum membrane was investigated using rapid filtration and light scattering assays. We found a protein-mediated, bi-directional, low-affinity, and high-capacity, facilitative sulfate transport in rat liver microsomes, which could be inhibited by the prototypical anion transport inhibitor, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. It was resistant to various phosphate transport inhibitors and was not influenced by high concentration of phosphate or pyrophosphate, which is contradictory to involvement of phosphate transporters. It was sensitive to S3483 that has been reported to inhibit the glucose 6-phosphate transporter (G6PT), but the weak competition between sulfate and glucose 6-phosphate did not confirm the participation of this transporter. Moreover, the comparison of the activity and S3483 sensitivity of sulfate transport in microsomes prepared from G6PT-overexpressing or wild type COS-7 cells did not show any significant difference. Our results indicate that sulfate fluxes in the endoplasmic reticulum are mediated by a novel, S3483-sensitive transport pathway(s). 相似文献