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991.
Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice 总被引:4,自引:0,他引:4
Turgeman G Zilberman Y Zhou S Kelly P Moutsatsos IK Kharode YP Borella LE Bex FJ Komm BS Bodine PV Gazit D 《Journal of cellular biochemistry》2002,86(3):461-474
Osteoporosis is a disease manifested in drastic bone loss resulting in osteopenia and high risk for fractures. This disease is generally divided into two subtypes. The first, post-menopausal (type I) osteoporosis, is primarily related to estrogen deficiency. The second, senile (type II) osteoporosis, is mostly related to aging. Decreased bone formation, as well as increased bone resorption and turnover, are thought to play roles in the pathophysiology of both types of osteoporosis. In this study, we demonstrate in murine models for both type I (estrogen deficiency) and type II (senile) osteopenia/osteoporosis that reduced bone formation is related to a decrease in adult mesenchymal stem cell (AMSC) number, osteogenic activity, and proliferation. Decreased proliferation is coupled with increased apoptosis in AMSC cultures obtained from osteopenic mice. Recombinant human bone morphogenetic protein (rhBMP-2) is a highly osteoinductive protein, promoting osteogenic differentiation of AMSCs. Systemic intra-peritoneal (i.p.) injections of rhBMP-2 into osteopenic mice were able to reverse this phenotype in the bones of these animals. Moreover, this change in bone mass was coupled to an increase in AMSCs numbers, osteogenic activity, and proliferation as well as a decrease in apoptosis. Bone formation activity was increased as well. However, the magnitude of this response to rhBMP-2 varied among different stains of mice. In old osteopenic BALB/c male mice (type II osteoporosis model), rhBMP-2 systemic treatment also restored both articular and epiphyseal cartilage width to the levels seen in young mice. In summary, our study shows that AMSCs are a good target for systemically active anabolic compounds like rhBMP-2. 相似文献
992.
Fabienne Billiard Sevasti Karaliota Bei Wang Dimitrios Stellas Ioannis Serafimidis Antigoni Manousopoulou Yiassemi Koutmani Elpiniki Ninou Jacquelynn Golubov Amanda DaNave Panagiotis Tsakanikas Yurong Xin Wen Zhang Matthew Sleeman George D. Yancopoulos Andrew J. Murphy Spiros D. Garbis Katia Karalis Dimitris Skokos 《Cell reports》2018,22(4):895-904
993.
Panagiota Kontou Athanasia Pavlopoulou Georgia Braliou Spyridoula Bogiatzi Niki Dimou Sripal Bangalore Pantelis Bagos 《BMC medical genomics》2018,11(1):109
Background
Myocardial infarction (MI) is a multifactorial disease with complex pathogenesis, mainly the result of the interplay of genetic and environmental risk factors. The regulation of thrombosis, inflammation and cholesterol and lipid metabolism are the main factors that have been proposed thus far to be involved in the pathogenesis of MI. Traditional risk-estimation tools depend largely on conventional risk factors but there is a need for identification of novel biochemical and genetic markers. The aim of the study is to identify differentially expressed genes that are consistently associated with the incidence myocardial infarction (MI), which could be potentially incorporated into the traditional cardiovascular diseases risk factors models.Methods
The biomedical literature and gene expression databases, PubMed and GEO, respectively, were searched following the PRISMA guidelines. The key inclusion criteria were gene expression data derived from case-control studies on MI patients from blood samples. Gene expression datasets regarding the effect of medicinal drugs on MI were excluded. The t-test was applied to gene expression data from case-control studies in MI patients.Results
A total of 162 articles and 174 gene expression datasets were retrieved. Of those a total of 4 gene expression datasets met the inclusion criteria, which contained data on 31,180 loci in 93 MI patients and 89 healthy individuals. Collectively, 626 differentially expressed genes were detected in MI patients as compared to non-affected individuals at an FDR q-value?=?0.01. Of those, 88 genes/gene products were interconnected in an interaction network. Totally, 15 genes were identified as hubs of the network.Conclusions
Functional enrichment analyses revealed that the DEGs and that they are mainly involved in inflammatory/wound healing, RNA processing/transport mechanisms and a yet not fully characterized pathway implicated in RNA transport and nuclear pore proteins. The overlap between the DEGs identified in this study and the genes identified through genetic-association studies is minimal. These data could be useful in future studies on the molecular mechanisms of MI as well as diagnostic and prognostic markers.994.
Ioannis Mitroulis Klara Ruppova Baomei Wang Lan-Sun Chen Michal Grzybek Tatyana Grinenko Anne Eugster Maria Troullinaki Alessandra Palladini Ioannis Kourtzelis Antonios Chatzigeorgiou Andreas Schlitzer Marc Beyer Leo A.B. Joosten Berend Isermann Mathias Lesche Andreas Petzold Kai Simons Triantafyllos Chavakis 《Cell》2018,172(1-2):147-161.e12
995.
Alexandra V. Chatzikonstantinou Maria V. Chatziathanasiadou Enrico Ravera Marco Fragai Giacomo Parigi Ioannis P. Gerothanassis Claudio Luchinat Haralambos Stamatis Andreas G. Tzakos 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(1):1-8
Background
Natural products offer a wide range of biological activities, but they are not easily integrated in the drug discovery pipeline, because of their inherent scaffold intricacy and the associated complexity in their synthetic chemistry. Enzymes may be used to perform regioselective and stereoselective incorporation of functional groups in the natural product core, avoiding harsh reaction conditions, several protection/deprotection and purification steps.Methods
Herein, we developed a three step protocol carried out inside an NMR-tube. 1st-step: STD-NMR was used to predict the: i) capacity of natural products as enzyme substrates and ii) possible regioselectivity of the biotransformations. 2nd-step: The real-time formation of multiple-biotransformation products in the NMR-tube bioreactor was monitored in-situ. 3rd-step: STD-NMR was applied in the mixture of the biotransformed products to screen ligands for protein targets.Results
Herein, we developed a simple and time-effective process, the “NMR-tube bioreactor”, that is able to: (i) predict which component of a mixture of natural products can be enzymatically transformed, (ii) monitor in situ the transformation efficacy and regioselectivity in crude extracts and multiple substrate biotransformations without fractionation and (iii) simultaneously screen for interactions of the biotransformation products with pharmaceutical protein targets.Conclusions
We have developed a green, time-, and cost-effective process that provide a simple route from natural products to lead compounds for drug discovery.General significanse
This process can speed up the most crucial steps in the early drug discovery process, and reduce the chemical manipulations usually involved in the pipeline, improving the environmental compatibility. 相似文献996.
Rob J. De Boer Alan S. Perelson Ioannis G. Kevrekidis 《Bulletin of mathematical biology》1993,55(4):745-780
We develop a model for the idiotypic interaction between two B cell clones. This model takes into account B cell proliferation,
B cell maturation, antibody production, the formation and subsequent elimination of antibody-antibody complexes and recirculation
of antibodies between the spleen and the blood. Here we investigate, by means of stability and bifurcation analysis, how each
of the processes influences the model's behavior. After appropriate nondimensinalization, the model consists of eight ordinary
differential equations and a number of parameters. We estimate the parameters from experimental sources. Using a coordinate
system that exploits the pairwise symmetry of the interactions between two clones, we analyse two simplified forms of the
model and obtain bifurcation diagrams showing how their five equilibrium states are related. We show that the so-called immune
states lose stability if B cell and antibody concentrations change on different time scales. Additionally, we derive the structure
of stable and unstable manifolds of saddle-tye equilibria, pinpoint their (global) bifurcations and show that these bifurcations
play a crucial role in determining the parameter regimes in which the model exhibits oscillatory behavior. 相似文献
997.
D. Dimou A.M. D'Onghia M. Laimer da amara Machado V. Savino 《Journal of Phytopathology》1994,142(3):258-262
A virus recovered by inoculation of sap from Austrian vines with yellow mosaic symptoms was compared with, and found virtually indistinguishable from, an authentic Hungarian isolate of grapevine chrome mosaic nepovirus. This seems to be the first record of the virus in Austria. 相似文献
998.
Serge Pieters David McGowan Florence Herschke Frederik Pauwels Bart Stoops Stefaan Last Werner Embrechts Annick Scholliers Wendy Mostmans Kris Van Dijck Bertrand Van Schoubroeck Tine Thoné Dorien De Pooter Gregory Fanning Mari Luz Rosauro Mourad Daoubi Khamlichi Ioannis Houpis Eric Arnoult Pierre Raboisson 《Bioorganic & medicinal chemistry letters》2018,28(4):711-719
The discovery of a novel series of highly potent quinazoline TLR 7/8 agonists is described. The synthesis and structure–activity relationship is presented. Structural requirements and optimization of this series toward TLR 7 selectivity afforded the potent agonist 48. Pharmacokinetic and pharmacodynamic studies highlighted 48 as an orally available endogenous interferon (IFN-α) inducer in mice. 相似文献
999.
Athanassios Stavrakoudis Ioannis N. Demetropoulos Constantinos Sakarellos Maria Sakarellos-Daitsiotis Vassilios Tsikaris 《Letters in Peptide Science》1997,4(4-6):481-487
The design, synthesis and catalytic properties of acyclic branched peptide carrier that possesses thecatalytic triad residues of the serine proteases isreported. The synthesis of the peptide model wastotally completed on solid support using threedifferent orthogonal amino protecting groups.Hydrolytic activity measurements againstSuc-Ala-Ala-Ala-pNA substrate showed that it ishydrolysed by the peptide model to a small extent.Despite this small hydrolytic activity, it is thefirst time, to our knowledge, that hydrolysis of such a substrate is reported by an enzyme model compound.Contrary, this enzyme model peptide showedconsiderable activity against the Boc-Ala-pNPsubstrate (kcat = 0.414 min–1 and Km = 0.228 mm). These results suggest that thedesigned carrier brings in appropriate contact thecatalytic triad residues (Ser, His, Asp) resulting inthe obtained hydrolytic activity. 相似文献
1000.
Heleen Demeyer Elena Gimeno-Santos Roberto A. Rabinovich Miek Hornikx Zafeiris Louvaris Willem I. de Boer Niklas Karlsson Corina de Jong Thys Van der Molen Ioannis Vogiatzis Wim Janssens Judith Garcia-Aymerich Thierry Troosters Michael I. Polkey PROactive consortium 《PloS one》2016,11(3)