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31.
Petek E Schwarzbraun T Noor A Patel M Nakabayashi K Choufani S Windpassinger C Stamenkovic M Robertson MM Aschauer HN Gurling HM Kroisel PM Wagner K Scherer SW Vincent JB 《Molecular genetics and genomics : MGG》2007,277(1):71-81
We recently reported the disruption of the inner mitochondrial membrane peptidase 2-like (IMMP2L) gene by a chromosomal breakpoint in a patient with Gilles de la Tourette syndrome (GTS). In the present study we sought
to identify genetic variation in IMMP2L, which, through alteration of protein function or level of expression might contribute to the manifestation of GTS. We screened
39 GTS patients, and, due to the localization of IMMP2L in the critical region for the autistic disorder (AD) locus on chromosome 7q (AUTS1), 95 multiplex AD families; however,
no coding mutations were found in either GTS or AD patients. In addition, no parental-specific expression of IMMP2L was detected in somatic cell hybrids containing human chromosome 7 and human cell lines carrying a maternal uniparental disomy
for chromosome 7 (mUPD7). Despite the fact that no deleterious mutations in IMMPL2 (other than the inverted duplication identified previously) were identified in either GTS or AD, this gene cannot be excluded
as a possible rare cause of either disorder. 相似文献
32.
Chiara Salvesi Stefania Silvi Dennis Fiorini Serena Scortichini Gianni Sagratini Francesco A. Palermo Renato De Leone Nadaniela Egidi Lorella Fatone Carlo Cifani Amedeo Amedei Francesca Scocchera Mara Morici Beatrice Gatto Fausto Mannucci Valerio Valeriani Marco Malavasi Sara Servili Andrea Casula Andrea Cresci Ivano Corradetti Francesco Carpi Matteo Picciolini Maria Magdalena Coman Maria Cristina Verdenelli 《Journal of applied microbiology》2022,133(5):2941-2953
33.
34.
Andreea A. Gheorghita Francis Wolfram Gregory B. Whitfield Holly M. Jacobs Roland Pfoh Steven S.Y. Wong Allison K. Guitor Mara C. Goodyear Alison M. Berezuk Cezar M. Khursigara Matthew R. Parsek P. Lynne Howell 《The Journal of biological chemistry》2022,298(2)
Pseudomonas aeruginosa is an opportunistic human pathogen and a leading cause of chronic infection in the lungs of individuals with cystic fibrosis. After colonization, P. aeruginosa often undergoes a phenotypic conversion to mucoidy, characterized by overproduction of the alginate exopolysaccharide. This conversion is correlated with poorer patient prognoses. The majority of genes required for alginate synthesis, including the alginate lyase, algL, are located in a single operon. Previous investigations of AlgL have resulted in several divergent hypotheses regarding the protein’s role in alginate production. To address these discrepancies, we determined the structure of AlgL and, using multiple sequence alignments, identified key active site residues involved in alginate binding and catalysis. In vitro enzymatic analysis of active site mutants highlights R249 and Y256 as key residues required for alginate lyase activity. In a genetically engineered P. aeruginosa strain where alginate biosynthesis is under arabinose control, we found that AlgL is required for cell viability and maintaining membrane integrity during alginate production. We demonstrate that AlgL functions as a homeostasis enzyme to clear the periplasmic space of accumulated polymer. Constitutive expression of the AlgU/T sigma factor mitigates the effects of an algL deletion during alginate production, suggesting that an AlgU/T-regulated protein or proteins can compensate for an algL deletion. Together, our study demonstrates the role of AlgL in alginate biosynthesis, explains the discrepancies observed previously across other P. aeruginosa ΔalgL genetic backgrounds, and clarifies the existing divergent data regarding the function of AlgL as an alginate degrading enzyme. 相似文献
35.
Denis Tvorogov Chloe A L ThompsonPeach Johannes Foßelteder Mara Dottore Frank Stomski Suraiya A Onnesha Kelly Lim Paul A B Moretti Stuart M Pitson David M Ross Andreas Reinisch Daniel Thomas Angel F Lopez 《EMBO reports》2022,23(4)
Calreticulin (CALR) is recurrently mutated in myelofibrosis via a frameshift that removes an endoplasmic reticulum retention signal, creating a neoepitope potentially targetable by immunotherapeutic approaches. We developed a specific rat monoclonal IgG2α antibody, 4D7, directed against the common sequence encoded by both insertion and deletion mutations. 4D7 selectively bound to cells co‐expressing mutant CALR and thrombopoietin receptor (TpoR) and blocked JAK‐STAT signalling, TPO‐independent proliferation and megakaryocyte differentiation of mutant CALR myelofibrosis progenitors by disrupting the binding of CALR dimers to TpoR. Importantly, 4D7 inhibited proliferation of patient samples with both insertion and deletion CALR mutations but not JAK2 V617F and prolonged survival in xenografted bone marrow models of mutant CALR‐dependent myeloproliferation. Together, our data demonstrate a novel therapeutic approach to target a problematic disease driven by a recurrent somatic mutation that would normally be considered undruggable. 相似文献
36.
Jada L-B Davis Mara OConnor Hannah Erlbacher Sarah L. Schlichte Hanna E. Stevens 《The Yale journal of biology and medicine》2022,95(1):87
Prenatal stress is a neuropsychiatric risk factor, and effects may be mediated by prenatal oxidative stress. Cell types in the brain sensitive to oxidative stress—cortical microglia and cortical and hippocampal interneurons—may be altered by oxidative stress generated during prenatal stress and may be neurobiological substrates for altered behavior. Our objective was to determine the critical nature of oxidative stress in prenatal stress effects by manipulating prenatal antioxidants. CD1 mouse dams underwent restraint embryonic day 12 to 18 three times daily or no stress and received intraperitoneal injections before each stress period of vehicle, N-acetylcysteine (200 mg/kg daily), or astaxanthin (30 mg/kg before first daily stress, 10 mg/kg before second/third stresses). Adult male and female offspring behavior, microglia, and interneurons were assessed. Results supported the hypothesis that prenatal stress-induced oxidative stress affects microglia; microglia ramification increased after prenatal stress, and both antioxidants prevented these effects. In addition, N-acetylcysteine or astaxanthin was effective in preventing distinct male and female interneuron changes; decreased female medial frontal cortical parvalbumin interneurons was prevented by either antioxidant; increased male medial frontal cortical parvalbumin interneurons was prevented by N-acetylcysteine and decreased male hippocampal GAD67GFP+ cells prevented by astaxanthin. Prenatal stress-induced increased anxiety-like behavior and decreased sociability were not prevented by prenatal antioxidants. Sensorimotor gating deficits in males was partially prevented by prenatal astaxanthin. This study demonstrates the importance of oxidative stress for persistent impacts on offspring cortical microglia and interneurons, but did not link these changes with anxiety-like, social, and sensorimotor gating behaviors. 相似文献
37.
Airam Rodríguez Juan J. Negro Mara Mulero Carlos Rodríguez Jesús Hernández-Pliego Javier Bustamante 《PloS one》2012,7(12)
Technological advances for wildlife monitoring have expanded our ability to study behavior and space use of many species. But biotelemetry is limited by size, weight, data memory and battery power of the attached devices, especially in animals with light body masses, such as the majority of bird species. In this study, we describe the combined use of GPS data logger information obtained from free-ranging birds, and environmental information recorded by unmanned aerial systems (UASs). As a case study, we studied habitat selection of a small raptorial bird, the lesser kestrel Falco naumanni, foraging in a highly dynamic landscape. After downloading spatio-temporal information from data loggers attached to the birds, we programmed the UASs to fly and take imagery by means of an onboard digital camera documenting the flight paths of those same birds shortly after their recorded flights. This methodology permitted us to extract environmental information at quasi-real time. We demonstrate that UASs are a useful tool for a wide variety of wildlife studies. 相似文献
38.
Waste of leaf-cutting ants: disposal,nest structure,and abiotic soil factors around internal waste chambers 总被引:1,自引:0,他引:1
Sandra S. Verza Eduardo A. Diniz Mara F. Chiarelli Rosilda M. Mussury Odair C. Bueno 《Acta ethologica》2017,20(2):119-126
Leaf-cutting ants produce large quantities of waste that harbor bacteria and fungi that are harmful to the colony. To be protected from these pathogens, the workers of Atta species present a sophisticated organization to manage harmful material, which can be deposited outside the nest or in internal chambers. However, little is known about the behavior of Acromyrmex species in handling and disposal of waste. Due to some observations, we assume that the same species of Acromyrmex can deposit waste outside the nest and into internal chambers and raise the following question: what determines the occurrence of internal waste chambers in Acromyrmex? To address this question, we verified whether nest depth influences the waste-chamber occurrence. We also verified the nest structure and the abiotic factors of soil beside each waste-chamber: pH and water content of the soil. For this, eight nests were excavated for Acromyrmex balzani and Acromyrmex rugosus rugosus. We verified that not only can the same leaf-cutting ant species deposit debris both outside and inside the nest but also the same nest can present internal chambers and external waste deposit. The soil beside the waste chamber always presented an acidic pH, while the humidity varied widely. Our results showed that the nest depth was highly correlated with the depth of the waste chamber (p = 0.0003) and probably has some influence on waste disposal. The characteristics of the nest and the role of depth in the choice of waste chamber location are discussed. 相似文献
39.
A simple model for evaluation of diffusion times of small molecule into protein crystals has been developed, which takes into account the physical and chemical properties both of protein crystal and the diffusing molecules. The model also includes consideration of binding and the binding affinity of a ligand to the protein. The model has been validated by simulation of experimental set-ups of several examples found in the literature. These experiments cover a wide range of situations: from small to relatively large diffusing molecules, crystals having low, medium, or high protein density, and different size. The reproduced experiments include ligand exchange in protein crystals by soaking techniques. Despite the simplifying assumptions of the model, theoretical and experimental data are in agreement with available data, with experimental diffusion times ranging from a few seconds to several hours. The method has been used successfully for planning intermediate cryotrapping experiments in maltodextrin phosphorylase crystals. 相似文献
40.
Rocchi MS Ballingall KT MacHugh ND McKeever DJ 《International journal for parasitology》2006,36(7):771-778
Theileriaparva is an intracellular protozoan parasite that causes a fatal lymphoproliferative disease of cattle known as East Coast Fever. The parasite infects host lymphocytes causing their transformation and uncontrolled proliferation. Infiltration of major organs with parasitized lymphoblasts results in most cases in death within 3 weeks. Although both T and B lymphocytes are susceptible to infection, the majority of cell lines arising from infection of peripheral blood mononuclear cells in vitro are of T cell lineage. To explore the basis of this phenotypic bias we have followed the very early stages of parasite development in vitro at the single cell level. Peripheral blood mononuclear cells were infected and stained for both surface phenotype and intracellular parasite antigen and analysed by flow cytometry. Although the parasite antigen was detected intracellularly as early as 6h p.i., our data indicate that parasite infection does not lead to cell transformation in all instances. Rather, specific cell types appear to undergo selection very early after infection and expansion of particular cell subsets results in survival and growth of only a small proportion of the cells originally parasitized. 相似文献