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61.
Caroline Comte Yann Tonin Anne-Marie Heckel-Mager Abdeldjalil Boucheham Alexandre Smirnov Karine Auré Anne Lombès Robert P. Martin Nina Entelis Ivan Tarassov 《Nucleic acids research》2013,41(1):418-433
Mitochondrial mutations, an important cause of incurable human neuromuscular diseases, are mostly heteroplasmic: mutated mitochondrial DNA is present in cells simultaneously with wild-type genomes, the pathogenic threshold being generally >70% of mutant mtDNA. We studied whether heteroplasmy level could be decreased by specifically designed oligoribonucleotides, targeted into mitochondria by the pathway delivering RNA molecules in vivo. Using mitochondrially imported RNAs as vectors, we demonstrated that oligoribonucleotides complementary to mutant mtDNA region can specifically reduce the proportion of mtDNA bearing a large deletion associated with the Kearns Sayre Syndrome in cultured transmitochondrial cybrid cells. These findings may be relevant to developing of a new tool for therapy of mtDNA associated diseases. 相似文献
62.
Aparecida de Lourdes Perim Roberta Losi Guembarovski Julie Massayo Maeda Oda Leandra Fiori Lopes Carolina Batista Ariza Marla Karine Amarante Maria Helena Pelegrinelli Fungaro Karen Brajão de Oliveira Maria Angelica Ehara Watanabe 《Molecular biology reports》2013,40(7):4591-4596
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Genetic polymorphisms in the 3′UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression. Thus the objective of the present study was to detect the frequency of two genetic polymorphisms in ALL patients and controls and to add information their impact on genetic susceptibility and prognosis. The CXCL12 and TP53 polymorphisms were tested in 54 ALL child patients and in 58 controls by restriction fragment length polymerase chain reaction and allelic specific chain reaction techniques, respectively. The frequencies of both allelic variants were higher in ALL patients than in the controls and indicated a positive association: OR = 2.44; 95 % CI 1.05–5.64 for CXCL12 and OR = 2.20; 95 % CI 1.03–4.70 for TP53. Furthermore, when the two genetic variants were analyzed together, they increased significantly more than fivefold the risk of this neoplasia development (OR = 5.24; 95 % CI 1.39–19.75), indicating their potential as susceptibility markers for ALL disease and the relevance of the allelic variant combination to increased risk of developing malignant tumors. Future studies may indicate a larger panel of genes involved in susceptibility of childhood ALL and other hematological neoplasias. 相似文献
63.
Jean‐François Bourzac Karine L'Ériger Jean‐François Larrivée Guillaume Arguin Maude S. Bilodeau Jana Stankova Fernand‐Pierre Gendron 《Journal of cellular physiology》2013,228(1):120-129
With the diabetes epidemic affecting the world population, there is an increasing demand for means to regulate glycemia. Dietary glucose is first absorbed by the intestine before entering the blood stream. Thus, the regulation of glucose absorption by intestinal epithelial cells (IECs) could represent a way to regulate glycemia. Among the molecules involved in glycemia homeostasis, extracellular ATP, a paracrine signaling molecule, was reported to induce insulin secretion from pancreatic β cells by activating P2Y and P2X receptors. In rat's jejunum, P2X7 expression was previously immunolocalized to the apex of villi, where it has been suspected to play a role in apoptosis. However, using an antibody recognizing the receptor extracellular domain and thus most of the P2X7 isoforms, we showed that expression of this receptor is apparent in the top two‐thirds of villi. These data suggest a different role for this receptor in IECs. Using the non‐cancerous IEC‐6 cells and differentiated Caco‐2 cells, glucose transport was reduced by more than 30% following P2X7 stimulation. This effect on glucose transport was not due to P2X7‐induced cell apoptosis, but rather was the consequence of glucose transporter 2 (Glut2)'s internalization. The signaling pathway leading to P2X7‐dependent Glut2 internalization involved the calcium‐independent activation of phospholipase Cγ1 (PLCγ1), PKCδ, and PKD1. Although the complete mechanism regulating Glut2 internalization following P2X7 activation is not fully understood, modulation of P2X7 receptor activation could represent an interesting approach to regulate intestinal glucose absorption. J. Cell. Physiol. 228: 120–129, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
64.
Alexandra M. Nicholson NiCole A. Finch Aleksandra Wojtas Matt C. Baker Ralph B. Perkerson III Monica Castanedes‐Casey Linda Rousseau Luisa Benussi Giuliano Binetti Roberta Ghidoni Ging‐Yuek R. Hsiung Ian R. Mackenzie Elizabeth Finger Bradley F. Boeve Nilüfer Ertekin‐Taner Neill R. Graff‐Radford Dennis W. Dickson Rosa Rademakers 《Journal of neurochemistry》2013,126(6):781-791
Frontotemporal lobar degeneration (FTLD) is the second leading cause of dementia in individuals under age 65. In many patients, the predominant pathology includes neuronal cytoplasmic or intranuclear inclusions of ubiquitinated TAR DNA binding protein 43 (FTLD‐TDP). Recently, a genome‐wide association study identified the first FTLD‐TDP genetic risk factor, in which variants in and around the TMEM106B gene (top SNP rs1990622) were significantly associated with FTLD‐TDP risk. Intriguingly, the most significant association was in FTLD‐TDP patients carrying progranulin (GRN) mutations. Here, we investigated to what extent the coding variant, rs3173615 (p.T185S) in linkage disequilibrium with rs1990622, affects progranulin protein (PGRN) biology and transmembrane protein 106 B (TMEM106B) regulation. First, we confirmed the association of TMEM106B variants with FTLD‐TDP in a new cohort of GRN mutation carriers. We next generated and characterized a TMEM106B‐specific antibody for investigation of this protein. Enzyme‐linked immunoassay analysis of progranulin protein levels showed similar effects upon T185 and S185 TMEM106B over‐expression. However, over‐expression of T185 consistently led to higher TMEM106B protein levels than S185. Cycloheximide treatment experiments revealed that S185 degrades faster than T185 TMEM106B, potentially due to differences in N‐glycosylation at residue N183. Together, our results provide a potential mechanism by which TMEM106B variants lead to differences in FTLD‐TDP risk.
65.
Thomas Silberfeld Lucie Bittner Cindy Fernández‐García Corinne Cruaud Florence Rousseau Bruno de Reviers Frederik Leliaert Claude E. Payri Olivier De Clerck 《Journal of phycology》2013,49(1):130-142
The brown algal genus Padina (Dictyotales, Phaeophyceae) is distributed worldwide in tropical and temperate seas. Global species diversity and distribution ranges, however, remain largely unknown. Species‐level diversity was reassessed using DNA‐based, algorithmic species delineation techniques based on cox3 and rbcL sequence data from 221 specimens collected worldwide. This resulted in estimates ranging from 39 to 61 putative species (ESUs), depending on the technique as well as the locus. We discuss the merits, potential pitfalls, and evolutionary and biogeographic significance of algorithmic species delineation. We unveil patterns whereby ESUs are in all but one case restricted to either the Atlantic or Indo‐Pacific Ocean. Within ocean basins we find evidence for the vast majority of ESUs to be confined to a single marine realm. Exceptions, whereby ESUs span up to three realms, are located in the Indo‐Pacific Ocean. Patterns of range‐restricted species likely arise by repeated founder events and subsequent peripatric speciation, hypothesized to dominate speciation mechanisms for coastal marine organisms in the Indo‐Pacific. Using a three‐gene (cox3, psaA and rbcL), relaxed molecular clock phylogenetic analysis we estimated divergence times, providing a historical framework to interpret biogeographic patterns. 相似文献
66.
Lisa Jacquin Claudy Haussy Claire Bertin Karine Laroucau Julien Gasparini 《Biological journal of the Linnean Society. Linnean Society of London》2013,108(3):647-657
Melanin‐based coloration is widespread among vertebrates, yet the adaptive significance of such pigments remains elusive, particularly with regard to the link between melanin and immune‐mediated maternal effects. The aim of this study was to investigate whether melanin‐based coloration could signal the ability of mothers to mount a humoral response and to transfer maternal antibodies (Ab) to their young. We injected differently coloured (pale and dark) female feral pigeons (Columba livia) with Chlamydiae (a natural antigen) and Keyhole Limpet Haemocyanin (KLH, an artificial antigen), and found no significant difference in humoral response between differently coloured females. However, darker females transferred more Ab against Chlamydiae into their eggs than paler ones, despite similar circulating levels of Ab. In addition to this, melanin‐based coloration showed a high heritability value. This suggests that a genetically based coloured trait might be linked to the ability of females to transfer specific Ab against Chlamydiae (but not against KLH) to their offspring, independent of their ability to produce Ab. This suggests that transmission of maternal Ab is antigen dependent, and that melanin‐based coloration might signal female ability to transmit specific Ab against natural pathogens. © 2013 The Linnean Society of London 相似文献
67.
Ingrid E. Alvial Karine Orth Bárbara C. Durán Evelyn Álvarez Francisco A. Squeo 《Hydrobiologia》2013,709(1):11-25
The ecology of macroinvertebrate communities in arid regions is still poorly understood. Here we examined how the community structure varied at spatial and temporal scales in streams and tributaries of the Huasco River in semi-arid region of Northern Chile. We expected that macroinvertebrate distribution may be responding to natural processes of mineralization described for Chilean semiarid basins. The relationships among biotic and abiotic variables were assessed through multivariate techniques (principal component analysis, non-metric multidimensional scaling, canonical correspondence analysis), and a two-way analysis of similarity was used to evaluate differences between basins and years (2007, 2008, and 2009). Significant differences in community structure and physical–chemical variables between basins (Del Carmen and Del Tránsito) were found, but not between years. Altitude, Mn, Al, Ca, Na, HCO3, and dissolved oxygen were the variables that best accounted for the communities distribution. In particular, high metals concentration in El Transito basin should determine low density and diversity of macroinvertebrates. Chironomidae, Ephydridae, and Glossiphoniidae were associated to waters with high metals content and acidic pH, whereas Baetidae, Hydroptilidae, and Blephariceridae were associated to sites with more favorable physical–chemical conditions. These results contribute to understand the ecological patterns of macroinvertebrates in arid regions and should lead to conservation and monitoring plans for this remote place. 相似文献
68.
Marco A. Biamonte Jutta Wanner Karine G. Le Roch 《Bioorganic & medicinal chemistry letters》2013,23(10):2829-2843
This digest covers some of the most relevant progress in malaria drug discovery published between 2010 and 2012. There is an urgent need to develop new antimalarial drugs. Such drugs can target the blood stage of the disease to alleviate the symptoms, the liver stage to prevent relapses, and the transmission stage to protect other humans. The pipeline for the blood stage is becoming robust, but this should not be a source of complacency, as the current therapies set a high standard. Drug discovery efforts directed towards the liver and transmission stages are in their infancy but are receiving increasing attention as targeting these stages could be instrumental in eradicating malaria. 相似文献
69.
Kurt G. Pike Karine Malagu Marc G. Hummersone Keith A. Menear Heather M.E. Duggan Sylvie Gomez Niall M.B. Martin Linette Ruston Sarah L. Pass Martin Pass 《Bioorganic & medicinal chemistry letters》2013,23(5):1212-1216
The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC50, led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21). 相似文献
70.
Cécile Echalier Soultan Al-Halifa Aude Kreiter Christine Enjalbal Pierre Sanchez Luisa Ronga Karine Puget Pascal Verdié Muriel Amblard Jean Martinez Gilles Subra 《Amino acids》2013,45(6):1395-1403
Despite correct purity of crude peptides prepared on trityl resin by Fmoc/tBu microwave assisted solid phase peptide synthesis, surprisingly, lower yields than those expected were obtained while preparing C-terminal acid peptides. This could be explained by cyclization/cleavage through diketopiperazine formation during the second amino acid deprotection and third amino acid coupling. However, we provide here evidence that this is not the case and that this yield loss was due to high temperature promoted hydrolysis of the 2-chlorotrityl ester, yielding premature cleavage of the C-terminal acid peptides. 相似文献