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991.
Marliete C. Costa Heliana de Barros Fernandes Gleisy K. N. Gonalves Anderson P. N. Santos Gabriella F. Ferreira Gustavo J. C. de Freitas Paulo H. F. do Carmo Jsy Hubner Elúzia C. P. Emídio Julliana R. A. Santos Jane L. dos Santos Adelina M. dos Reis Caio T. Fagundes Aristbolo M. da Silva Daniel A. Santos 《Cellular microbiology》2020,22(6)
Cryptococcus gattii (Cg) is one of the agents of cryptococcosis, a severe systemic mycosis with a higher prevalence in men than women, but the influence of the female sex hormone, 17‐β‐estradiol (E2), on cryptococcosis remains unclear. Our study shows that female mice presented delayed mortality, increased neutrophil recruitment in bronchoalveolar lavage fluid, and reduced fungal load after 24 hr of infection compared to male and ovariectomised female mice (OVX). E2 replacement restored OVX female survival. Female macrophages have more efficient fungicidal activity, which was increased by E2 and reversed by the antagonist of G‐protein‐coupled oestrogen receptor (GPER), which negatively modulates PI3K activation. Furthermore, E2 induces a reduction in Cg cell diameter, cell charge, and antioxidant peroxidase activity. In conclusion, female mice present improved control of Cg infection, and GPER is important for E2 modulation of the female response. 相似文献
992.
993.
Henry T. Robertson Gustavo de los Campos David B. Allison 《Obesity (Silver Spring, Md.)》2013,21(2):398-404
Objective:
We demonstrate the utility of parametric survival analysis. The analysis of longevity as a function of risk factors such as body mass index (BMI; kg/m2), activity levels, and dietary factors is a mainstay of obesity research. Modeling survival through hazard functions, relative risks, or odds of dying with methods such as Cox proportional hazards or logistic regression are the most common approaches and have many advantages. However, they also have disadvantages in terms of the ease of interpretability, especially for non‐statisticians; the need for additional data to convert parameter estimates to estimates of years of life lost (YLL); debates about the appropriate time scale in the model; and an inability to estimate median survival time when the censoring rate is too high.Design and Methods:
We will conduct parametric survival analyses with multiple distributions, including distributions that are known to be poor fits (Gaussian), as well as a newly discovered “Compressed Gaussian”'' distribution.Results:
Parametric survival analysis models were able to accurately estimate median survival times in a population‐based data set of 15,703 individuals, even for distributions that were not good fits and the censoring rate was high, due to the central limit theorem.Conclusions:
Parametric survival models are able to provide more direct answers, and in our analysis of an obesity‐related data set, gave consistent YLL estimates regardless of the distribution used. We recommend increased consideration of parametric survival models in chronic disease and risk factor epidemiology. 相似文献994.
Nelly Mezzaroba Sonia Zorzet Erika Secco Stefania Biffi Claudio Tripodo Marco Calvaruso Ramiro Mendoza-Maldonado Sara Capolla Marilena Granzotto Ruben Spretz Gustavo Larsen Sandra Noriega Marianna Lucafò Eduardo Mansilla Chiara Garrovo Gustavo H. Marín Gabriele Baj Valter Gattei Gabriele Pozzato Luis Nú?ez Paolo Macor 《PloS one》2013,8(9)
995.
Juan Gerez Mariana Fuertes Lucas Tedesco Susana Silberstein Gustavo Sevlever Marcelo Paez-Pereda Florian Holsboer Adrián G. Turjanski Eduardo Arzt 《PloS one》2013,8(2)
RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, four splice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domain that is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparative studies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. We also demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-κB signaling pathway is inhibited and the HIF-1 pathway is increased more efficiently by the longest RSUME, by means of a greater physical interaction of RSUME267 with the target proteins. In addition, the mRNA and protein levels of these isoforms differ in human glioma samples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in most but not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway. However, the increased inhibition conferred by RSUME267 over the NF-κB signaling pathway, the increased activation over the HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform which may be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas. 相似文献
996.
Dorothée Sturm Lorella Marselli Florian Ehehalt Daniela Richter Marius Distler Stephan Kersting Robert Grützmann Krister Bokvist Philippe Froguel Robin Liechti Anne J?rns Paolo Meda Gustavo Bruno Baretton Hans-Detlev Saeger Anke M. Schulte Piero Marchetti Michele Solimena 《Journal of visualized experiments : JoVE》2013,(71)
997.
Gustavo A. Santos Vinícius D. Pereira Erika A. F. R. Roman Leticia Ignacio-Souza Daniele C. Vitorino Rodrigo Ferreira de Moura Daniela S. Razolli Adriana S. Torsoni Licio A. Velloso Marcio A. Torsoni 《PloS one》2013,8(4)
Background
Hypothalamic AMPK acts as a cell energy sensor and can modulate food intake, glucose homeostasis, and fatty acid biosynthesis. Intrahypothalamic fatty acid injection is known to suppress liver glucose production, mainly by activation of hypothalamic ATP-sensitive potassium (K(ATP)) channels. Since all models employed seem to involve malonyl-CoA biosynthesis, we hypothesized that acetyl-CoA carboxylase can modulate the counter-regulatory response independent of nutrient availability.Methodology/Principal Findings
In this study employing immunoblot, real-time PCR, ELISA, and biochemical measurements, we showed that reduction of the hypothalamic expression of acetyl-CoA carboxylase by antisense oligonucleotide after intraventricular injection increased food intake and NPY mRNA, and diminished the expression of CART, CRH, and TRH mRNA. Additionally, as in fasted rats, in antisense oligonucleotide-treated rats, serum glucagon and ketone bodies increased, while the levels of serum insulin and hepatic glycogen diminished. The reduction of hypothalamic acetyl-CoA carboxylase also increased PEPCK expression, AMPK phosphorylation, and glucose production in the liver. Interestingly, these effects were observed without modification of hypothalamic AMPK phosphorylation.Conclusion/Significance
Hypothalamic ACC inhibition can activate hepatic counter-regulatory response independent of hypothalamic AMPK activation. 相似文献998.
Julie A. Wallace Fu Li Subhasree Balakrishnan Carmen Z. Cantemir-Stone Thierry Pecot Chelsea Martin Raleigh D. Kladney Sudarshana M. Sharma Anthony J. Trimboli Soledad A. Fernandez Lianbo Yu Thomas J. Rosol Paul C. Stromberg Robert Lesurf Michael Hallett Morag Park Gustavo Leone Michael C. Ostrowski 《PloS one》2013,8(8)
Tumor fibroblasts are active partners in tumor progression, but the genes and pathways that mediate this collaboration are ill-defined. Previous work demonstrates that Ets2 function in stromal cells significantly contributes to breast tumor progression. Conditional mouse models were used to study the function of Ets2 in both mammary stromal fibroblasts and epithelial cells. Conditional inactivation of Ets2 in stromal fibroblasts in PyMT and ErbB2 driven tumors significantly reduced tumor growth, however deletion of Ets2 in epithelial cells in the PyMT model had no significant effect. Analysis of gene expression in fibroblasts revealed a tumor- and Ets2-dependent gene signature that was enriched in genes important for ECM remodeling, cell migration, and angiogenesis in both PyMT and ErbB2 driven-tumors. Consistent with these results, PyMT and ErbB2 tumors lacking Ets2 in fibroblasts had fewer functional blood vessels, and Ets2 in fibroblasts elicited changes in gene expression in tumor endothelial cells consistent with this phenotype. An in vivo angiogenesis assay revealed the ability of Ets2 in fibroblasts to promote blood vessel formation in the absence of tumor cells. Importantly, the Ets2-dependent gene expression signatures from both mouse models were able to distinguish human breast tumor stroma from normal stroma, and correlated with patient outcomes in two whole tumor breast cancer data sets. The data reveals a key function for Ets2 in tumor fibroblasts in signaling to endothelial cells to promote tumor angiogenesis. The results highlight the collaborative networks that orchestrate communication between stromal cells and tumor cells, and suggest that targeting tumor fibroblasts may be an effective strategy for developing novel anti-angiogenic therapies. 相似文献
999.
Intensive surveys have been conducted to unravel spatial patterns of benthic infauna communities. Although it has been recognized that benthic organisms are spatially structured along the horizontal and vertical dimensions of the sediment, little is known on how these two dimensions interact with each other. In this study we investigated the interdependence between the vertical and horizontal dimensions in structuring marine nematodes assemblages. We tested whether the similarity in nematode species composition along the horizontal dimension was dependent on the vertical layer of the sediment. To test this hypothesis, three-cm interval sediment samples (15 cm depth) were taken independently from two bedforms in three estuaries. Results indicated that assemblages living in the top layers are more abundant, species rich and less variable, in terms of species presence/absence and relative abundances, than assemblages living in the deeper layers. Results showed that redox potential explained the greatest amount (12%) of variability in species composition, more than depth or particle size. The fauna inhabiting the more oxygenated layers were more homogeneous across the horizontal scales than those from the reduced layers. In contrast to previous studies, which suggested that reduced layers are characterized by a specific set of tolerant species, the present study showed that species assemblages in the deeper layers are more causal (characterized mainly by vagrant species). The proposed mechanism is that at the superficial oxygenated layers, species have higher chances of being resuspended and displaced over longer distances by passive transport, while at the deeper anoxic layers they are restricted to active dispersal from the above and nearby sediments. Such restriction in the dispersal potential together with the unfavorable environmental conditions leads to randomness in the presence of species resulting in the high variability between assemblages along the horizontal dimension. 相似文献
1000.
Noelia Losino Ariel Waisman Claudia Solari Carlos Luzzani Darío Fernández Espinosa Alina Sassone Andrés F. Muro Santiago Miriuka Gustavo Sevlever Lino Bara?ao Alejandra Guberman 《PloS one》2013,8(11)
Embryonic stem cells (ESC) need a set of specific factors to be propagated. They can also grow in conditioned medium (CM) derived from a bovine granulosa cell line BGC (BGC-CM), a medium that not only preserves their main features but also increases ESC´s proliferation rate. The mitogenic properties of this medium were previously reported, ascribing this effect to an alternative spliced generated fibronectin isoform that contains the extra domain A (FN EDA+). Here, we investigated if the FN EDA+ isoform increased proliferation of mouse and human ES cells. We analyzed cell proliferation using conditioned media produced by different mouse embryonic fibroblast (MEF) lines genetically engineered to express FN constitutively including or excluding the EDA domain (FN EDA-), and in media supplemented with recombinant peptides containing or not the EDA. We found that the presence of EDA in the medium increased mouse and human ESC’s proliferation rate. Here we showed for the first time that this FN isoform enhances ESC’s proliferation. These findings suggest a possible conserved behavior for regulation of ES cells proliferation by this FN isoform and could contribute to improve their culturing conditions both for research and cell therapy. 相似文献