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121.
Leonardo Magno Rambo Leandro Rodrigo Ribeiro Iuri Domingues Della-Pace Daniel Neis Stamm Rogério da Rosa Gerbatin Marina Prigol Simone Pinton Cristina Wayne Nogueira Ana Flávia Furian Mauro Schneider Oliveira Michele Rechia Fighera Luiz Fernando Freire Royes 《Amino acids》2013,44(3):857-868
A growing body of evidence indicates that creatine (Cr) exerts beneficial effects on a variety of pathologies where energy metabolism and oxidative stress play an etiological role. However, the benefits of Cr treatment for epileptics are still shrouded in controversy. In the present study, we found that acute Cr treatment (300 mg/kg, p.o.) prevented the increase in electroencephalographic wave amplitude typically elicited by PTZ (30, 45 or 60 mg/kg, i.p.). Cr treatment also increased the latency periods of first myoclonic jerks, lengthened the latency periods of the generalized tonic–clonic seizures and reduced the time spent in the generalized tonic–clonic seizures induced by PTZ (60 mg/kg). Administration of PTZ (all doses) decreased Na+, K+-ATPase activity as well as adenosine triphosphate (ATP) and adenosine diphosphate levels in the cerebral cortex, but Cr treatment prevented these effects. Cr administration also prevented increases in xanthine oxidase activity, adenosine monophosphate levels, adenosine levels, inosine levels and uric acid levels that normally occur after PTZ treatment (60 mg/kg, i.p.). We also showed that Cr treatment increased the total Cr (Cr + PCr) content, creatine kinase activity and the mitochondrial membrane potential (ΔΨ) in the cerebral cortex. In addition, Cr prevented PTZ-induced mitochondrial dysfunction characterized by decreasing ΔΨ, increasing thiobarbituric acid-reactive substance levels and increasing protein carbonylation. These experimental findings reinforce the idea that mitochondrial dysfunction plays a critical role in models of epileptic seizures and suggest that buffering brain energy levels through Cr treatment may be a promising therapeutic approach for the treatment of this neurological disease. 相似文献
122.
Silvio Schueler Stefan Kapeller Heino Konrad Thomas Geburek Michael Mengl Michele Bozzano Jarkko Koskela François Lefèvre Jason Hubert Hojka Kraigher Roman Longauer Ditte C. Olrik 《Biodiversity and Conservation》2013,22(5):1151-1166
Genetic resources of forest trees are considered as a key factor for the persistence of forest ecosystems because the ability of tree species to survive under changing climate depends strongly on their intraspecific variation in climate response. Therefore, utilizing available genetic variation in climate response and planting alternative provenances suitable for future climatic conditions is considered as an important adaptation measure for forestry. On the other hand, the distribution of adaptive genetic diversity of many tree species is still unknown and the predicted shift of ecological zones and species’ distribution may threaten forest genetic resources that are important for adaptation. Here, we use Norway spruce in Austria as a case study to demonstrate the genetic variation in climate response and to analyse the existing network of genetic conservation units for its effectiveness to safeguard the hotspots of adaptive and neutral genetic diversity of this species. An analysis of the climate response of 480 provenances, clustered into 9 groups of climatically similar provenances, revealed high variation among provenance groups. The most productive and promising provenance clusters for future climates originate from three regions that today depict the warmest and driest areas of the natural spruce distribution in Austria. Gap analysis of the Austrian genetic conservation units in the EUFGIS Portal suggests adequate coverage of the genetic hotspots in southern parts of Austria, but not in eastern and northern Austria. Therefore conservation measures and sustainable utilization of the valuable genetic resources in these regions need to be expanded to cover their high adaptive genetic variation and local adaptation to a warmer climate. The study shows that current conservation efforts need to be evaluated for their effectiveness to protect genetic resources that are important for the survival of trees in a future climate. 相似文献
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125.
Stephen P. Slocombe QianYi Zhang Kenneth D. Black John G. Day Michele S. Stanley 《Journal of applied phycology》2013,25(4):961-972
The phenotypic and phylogenetic diversity of micro-algae capable of accumulating triacylglycerols provides a challenge for the accurate determination of biotechnological potential. High-yielding strains are needed to improve economic viability and their compositional information is required for optimizing biodiesel properties. To facilitate a high-throughput screening programme, a very rapid direct-derivatization procedure capable of extracting lyophilized material for GC analysis was compared with a scaled-down Folch-based method. This was carried out on ten micro-algal strains from 6 phyla where the more rapid direct-derivatization approach was found to provide a more reliable measure of yield. The modified Folch-based procedure was found to substantially underestimate oil yield in one Chlorella species (P?<?0.01). In terms of fatty acid composition however, the Folch procedure proved to be slightly better in recovering polyunsaturated fatty acids, in six out of the ten strains. Therefore, direct-derivatization is recommended for rapid determination of yields in screening approaches but can provide slightly less compositional accuracy than solvent-based extraction methods. 相似文献
126.
Michele Tinti Lars Kiemer Stefano Costa Martin L. Miller Francesca Sacco Jesper V. Olsen Martina Carducci Serena Paoluzi Francesca Langone Christopher T. Workman Nikolaj Blom Kazuya Machida Christopher M. Thompson Mike Schutkowski Søren Brunak Matthias Mann Bruce J. Mayer Luisa Castagnoli Gianni Cesareni 《Cell reports》2013,3(4):1293-1305
Highlights? The recognition specificity of 70 SH2 domains is probed ? Recognition specificity diverges faster than sequence ? PepspotDB is a database of protein interactions mediated by SH2 domains 相似文献
127.
Dian J. Chiang Sanjoy Roychowdhury Katelyn Bush Megan R. McMullen Sorana Pisano Kathryn Niese Mitchell A. Olman Michele T. Pritchard Laura E. Nagy 《PloS one》2013,8(7)
The effect of moderate alcohol consumption on liver fibrosis is not well understood, but evidence suggests that adenosine may play a role in mediating the effects of moderate ethanol on tissue injury. Ethanol increases the concentration of adenosine in the liver. Adenosine 2A receptor (A2AR) activation is known to enhance hepatic stellate cell (HSC) activation and A2AR deficient mice are protected from fibrosis in mice. Making use of a novel mouse model of moderate ethanol consumption in which female C57BL/6J mice were allowed continued access to 2% (vol/vol) ethanol (11% calories) or pair-fed control diets for 2 days, 2 weeks or 5 weeks and superimposed with exposure to CCl4, we tested the hypothesis that moderate ethanol consumption increases fibrosis in response to carbon tetrachloride (CCl4) and that treatment of mice with an A2AR antagonist prevents and/or reverses this ethanol-induced increase in liver fibrosis. Neither the expression or activity of CYP2E1, required for bio-activation of CCl4, nor AST and ALT activity in the plasma were affected by ethanol, indicating that moderate ethanol did not increase the direct hepatotoxicity of CCl4. However, ethanol feeding enhanced HSC activation and exacerbated liver fibrosis upon exposure to CCl4. This was associated with an increased sinusoidal angiogenic response in the liver. Treatment with A2AR antagonist both prevented and reversed the ability of ethanol to exacerbate liver fibrosis.
Conclusion
Moderate ethanol consumption exacerbates hepatic fibrosis upon exposure to CCl4. A2AR antagonism may be a potential pharmaceutical intervention to decrease hepatic fibrosis in response to ethanol. 相似文献128.
Vonn Walter Xiaoying Yin Matthew D. Wilkerson Christopher R. Cabanski Ni Zhao Ying Du Mei Kim Ang Michele C. Hayward Ashley H. Salazar Katherine A. Hoadley Karen Fritchie Charles G. Sailey Mark C. Weissler William W. Shockley Adam M. Zanation Trevor Hackman Leigh B. Thorne William D. Funkhouser Kenneth L. Muldrew Andrew F. Olshan Scott H. Randell Fred A. Wright Carol G. Shores D. Neil Hayes 《PloS one》2013,8(2)
Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented. 相似文献
129.
Cristina Zennaro Maria Pia Rastaldi Lorella Pascolo Marco Stebel Elisa Trevisan Mary Artero Claudio Tiribelli Vittorio Di Maso Michele Carraro 《PloS one》2013,8(6)
Several complex mechanisms contribute to the maintenance of the intricate ramified morphology of glomerular podocytes and to interactions with neighboring cells and the underlying basement membrane. Recently, components of small molecule transporter families have been found in the podocyte membrane, but expression and function of membrane transporters in podocytes is largely unexplored. To investigate this complex field of investigation, we used two molecules which are known substrates of membrane transporters, namely Penicillin G and Puromycin Aminonucleoside (PA).We observed that Penicillin G pre-administration prevented both in vitro and in vivo podocyte damage caused by PA, suggesting the engagement of the same membrane transporters by the two molecules. Indeed, we found that podocytes express a series of transporters which are known to be used by Penicillin G, such as members of the Organic Anion Transporter Polypeptides (OATP/Oatp) family of influx transporters, and P-glycoprotein, a member of the MultiDrug Resistance (MDR) efflux transporter family.Expression of OATP/Oatp transporters was modified by PA treatment. Similarly, in vitro PA treatment increased mRNA and protein expression of P-glycoprotein, as well as its activity, confirming the engagement of the molecule upon PA administration.In summary, we have characterized some of the small molecule transporters present at the podocyte membrane, focusing on those used by PA to enter and exit the cell. Further investigation will be needed to understand precisely the role of these transporter families in maintaining podocyte homeostasis and in the pathogenesis of podocyte injury. 相似文献
130.
Hassan Mahomed Rodney Ehrlich Tony Hawkridge Mark Hatherill Lawrence Geiter Fazlin Kafaar Deborah Ann Abrahams Humphrey Mulenga Michele Tameris Hennie Geldenhuys Willem Albert Hanekom Suzanne Verver Gregory Dudley Hussey 《PloS one》2013,8(3)