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131.
Ostapienko Borys I. Lopez Domenico Komarova Svetlana V. 《Biomechanics and modeling in mechanobiology》2019,18(2):277-289
Biomechanics and Modeling in Mechanobiology - Biologically guided precipitation of calcium phosphates is important for the formation of calcified human tissues, such as bone and teeth, and is of... 相似文献
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Breanna S. Borys Tania So Erin L. Roberts Leah Ferrie Leila Larijani Brett Abraham Roman Krawetz Derrick E. Rancourt Michael S. Kallos 《Biotechnology and bioengineering》2020,117(5):1316-1328
Embryonic stem cells (ESCs) have almost unlimited proliferation capacity in vitro and can retain the ability to contribute to all cell lineages, making them an ideal platform material for cell-based therapies. ESCs are traditionally cultured in static flasks on a feeder layer of murine embryonic fibroblast cells. Although sufficient to generate cells for research purposes, this approach is impractical to achieve large quantities for clinical applications. In this study, we have developed protocols that address a variety of challenges that currently bottleneck clinical translation of ESCs expanded in stirred suspension bioreactors. We demonstrated that mouse ESCs (mESCs) cryopreserved in the absence of feeder cells could be thawed directly into stirred suspension bioreactors at extremely low inoculation densities (100 cells/ml). These cells sustained proliferative capacity through multiple passages and various reactor sizes and geometries, producing clinically relevant numbers (109 cells) and maintaining pluripotency phenotypic and functional properties. Passages were completed in stirred suspension bioreactors of increasing scale, under defined batch conditions which greatly improved resource efficiency. Output mESCs were analyzed for pluripotency marker expression (SSEA-1, SOX-2, and Nanog) through flow cytometry, and spontaneous differentiation and teratoma analysis was used to demonstrate functional maintenance of pluripotency. 相似文献
134.
Nathan V. Whelan Matthew P. Galaska Breanna N. Sipley Jennifer M. Weber Paul D. Johnson Kenneth M. Halanych Brian S. Helms 《Molecular ecology》2019,28(7):1593-1610
Within riverine systems, headwater populations are hypothesized to harbour higher amounts of genetic distinctiveness than populations in the main stem of a river and display increased genetic diversity in large, downstream habitats. However, these hypotheses were mostly developed with insects and fish, and they have not been tested on many invertebrate lineages. Pleuroceridae gastropods are of particular ecological importance to rivers of eastern North America, sometimes comprising over 90% of macroinvertebrate biomass. Yet, virtually nothing is known of pleurocerid landscape genetics, including whether genetic diversity follows predictions made by hypotheses developed on more mobile species. Moreover, the commonly repeated hypothesis that intraspecific morphological variation in gastropods results from ecophenotypic plasticity has not been well tested on pleurocerids. Using 2bRAD‐seq to discover single nucleotide polymorphisms, we show that the threatened, Cahaba River endemic pleurocerid, Leptoxis ampla, has limited gene flow among populations and that migration is downstream‐biased, conflicting with previous hypotheses. Both tributary and main stem populations harbour unique genomic profiles, and genetic diversity was highest in downstream populations. Furthermore, L. ampla shell morphology was more correlated with genetic differences among individuals and populations than habitat characteristics. We anticipate similar genetic and demographic patterns to be seen in other pleurocerids, and hypotheses about gene flow and population demographics that were based on more mobile taxa often, but not always, apply to freshwater gastropods. From a conservation standpoint, genetic structure of L. ampla populations suggests distinctive genetic diversity is lost with localized extirpation, a phenomenon common across the range of Pleuroceridae. 相似文献
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Alexandra Melton Lara A. Doyle-Meyers Robert V. Blair Cecily Midkiff Hunter J. Melton Kasi Russell-Lodrigue Pyone P. Aye Faith Schiro Marissa Fahlberg Dawn Szeltner Skye Spencer Brandon J. Beddingfield Kelly Goff Nadia Golden Toni Penney Breanna Picou Krystle Hensley Kristin E. Chandler Jessica A. Plante Kenneth S. Plante Scott C. Weaver Chad J. Roy James A. Hoxie Hongmei Gao David C. Montefiori Joseph L. Mankowski Rudolf P. Bohm Jay Rappaport Nicholas J. Maness 《PLoS pathogens》2021,17(12)
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics. 相似文献
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Breanna M. Scorza Kurayi G. Mahachi Arin C. Cox Angela J. Toepp Adam Leal-Lima Anurag Kumar Kushwaha Patrick Kelly Claudio Meneses Geneva Wilson Katherine N. Gibson-Corley Lyric Bartholomay Shaden Kamhawi Christine A. Petersen 《PLoS neglected tropical diseases》2021,15(10)
BackgroundDogs are the primary reservoir for human visceral leishmaniasis due to Leishmania infantum. Phlebotomine sand flies maintain zoonotic transmission of parasites between dogs and humans. A subset of dogs is infected transplacentally during gestation, but at what stage of the clinical spectrum vertically infected dogs contribute to the infected sand fly pool is unknown.Methodology/Principal findingsWe examined infectiousness of dogs vertically infected with L. infantum from multiple clinical states to the vector Lutzomyia longipalpis using xenodiagnosis and found that vertically infected dogs were infectious to sand flies at differing rates. Dogs with mild to moderate disease showed significantly higher transmission to the vector than dogs with subclinical or severe disease. We documented a substantial parasite burden in the skin of vertically infected dogs by RT-qPCR, despite these dogs not having received intradermal parasites via sand flies. There was a highly significant correlation between skin parasite burden at the feeding site and sand fly parasite uptake. This suggests dogs with high skin parasite burden contribute the most to the infected sand fly pool. Although skin parasite load and parasitemia correlated with one another, the average parasite number detected in skin was significantly higher compared to blood in matched subjects. Thus, dermal resident parasites were infectious to sand flies from dogs without detectable parasitemia.Conclusions/SignificanceTogether, our data implicate skin parasite burden and earlier clinical status as stronger indicators of outward transmission potential than blood parasite burden. Our studies of a population of dogs without vector transmission highlights the need to consider canine vertical transmission in surveillance and prevention strategies. 相似文献
139.
Aranibar N Borys M Mackin NA Ly V Abu-Absi N Abu-Absi S Niemitz M Schilling B Li ZJ Brock B Russell RJ Tymiak A Reily MD 《Journal of biomolecular NMR》2011,49(3-4):195-206
NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a quantum mechanical total line shape analysis were utilized to quantify 30 metabolites such as amino acids, Krebs cycle intermediates, activated sugars, cofactors, and others in both media and cell extracts. The impact of bioreactor scale and addition of anti-apoptotic agents to the media on the extracellular and intracellular metabolome indicated changes in metabolic pathways of energy utilization. These results shed light into culture parameters that can be manipulated to optimize growth and protein production. Second, metabolomic analysis was performed on the superfusion media in a common model used for drug metabolism and toxicology studies, in vitro liver slices. In this study, it is demonstrated that two of the 48 standard media components, choline and histidine are depleted at a faster rate than many other nutrients. Augmenting the starting media with extra choline and histidine improves the long-term liver slice viability as measured by higher tissues levels of lactate dehydrogenase (LDH), glutathione and ATP, as well as lower LDH levels in the media at time points out to 94?h after initiation of incubation. In both models, media components and cellular metabolites are measured over time and correlated with currently accepted endpoint measures. 相似文献
140.
Miguel W. Tregnaghi Xavier Sáez-Llorens Pio López Hector Abate Enrique Smith Adriana Pósleman Arlene Calvo Digna Wong Carlos Cortes-Barbosa Ana Ceballos Marcelo Tregnaghi Alexandra Sierra Mirna Rodriguez Marisol Troiti?o Carlos Carabajal Andrea Falaschi Ana Leandro Maria Mercedes Castrejón Alejandro Lepetic Patricia Lommel William P. Hausdorff Dorota Borys Javier Ruiz Gui?azú Eduardo Ortega-Barría Juan P. Yarzábal Lode Schuerman COMPAS Group 《PLoS medicine》2015,12(6)