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Comparison of the three-dimensional structure of hyperthermophilic and mesophilic β-glycosidases shows differences in secondary
structure composition. The enzymes from hyperthermophilic archaea have a significantly larger number of β-strands arranged
in supernumerary β-sheets compared to mesophilic enzymes from bacteria and other organisms. Amino acid replacements designed
to alter the structure of the supernumerary β-strands were introduced by site directed mutagenesis into the sequence encoding
the β-glycosidase from Sulfolobus solfataricus. Most of the replacements caused almost complete loss of activity but some yielded enzyme variants whose activities were
affected specifically at higher temperatures. Far-UV CD spectra recorded as a function of temperature for both wild type β-glycosidase
and mutant V349G, one of the mutants with reduced activity at higher temperatures, were similar, showing that the protein
structure of the mutant was stable at the highest temperatures assayed. The properties of mutant V349G show a difference between
thermostability (stability of the protein structure at high temperatures) and thermophilicity (optimal activity at high temperatures). 相似文献
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Arias-Real Rebeca Gutirrez-Cnovas Cayetano Muoz Isabel Pascoal Cludia Menndez Margarita 《Ecosystems》2022,25(4):780-794
Ecosystems - Investigating the influence of biodiversity on ecosystem functioning over environmental gradients is needed to anticipate ecosystem responses to global change. However, our... 相似文献
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Grabeklis Andrey R. Skalny Anatoly V. Skalnaya Anastasia A. Zhegalova Irina V. Notova Svetlana V. Mazaletskaya Anna L. Skalnaya Margarita G. Tinkov Alexey A. 《Biological trace element research》2019,187(1):230-242
Biological Trace Element Research - Chronic exposure to lead causes disruption to energy production mechanisms and tissue damage, in particular through its binding to thiol groups and competition... 相似文献
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Margarita Medina‐Romero Andrew O'Reilly‐Nugent Anthony Davidson Jonathan Bray Elizabeth Wandrag Bernd Gruber Angelica Lopez‐Aldana Rakhi Palit Tim Reid Aaron Adamack Rod Pietsch Chris Allen Ralph Mac Nally Richard P. Duncan 《Ecography》2019,42(9):1514-1522
Imperfect detection can bias estimates of site occupancy in ecological surveys but can be corrected by estimating detection probability. Time‐to‐first‐detection (TTD) occupancy models have been proposed as a cost–effective survey method that allows detection probability to be estimated from single site visits. Nevertheless, few studies have validated the performance of occupancy‐detection models by creating a situation where occupancy is known, and model outputs can be compared with the truth. We tested the performance of TTD occupancy models in the face of detection heterogeneity using an experiment based on standard survey methods to monitor koala Phascolarctos cinereus populations in Australia. Known numbers of koala faecal pellets were placed under trees, and observers, uninformed as to which trees had pellets under them, carried out a TTD survey. We fitted five TTD occupancy models to the survey data, each making different assumptions about detectability, to evaluate how well each estimated the true occupancy status. Relative to the truth, all five models produced strongly biased estimates, overestimating detection probability and underestimating the number of occupied trees. Despite this, goodness‐of‐fit tests indicated that some models fitted the data well, with no evidence of model misfit. Hence, TTD occupancy models that appear to perform well with respect to the available data may be performing poorly. The reason for poor model performance was unaccounted for heterogeneity in detection probability, which is known to bias occupancy‐detection models. This poses a problem because unaccounted for heterogeneity could not be detected using goodness‐of‐fit tests and was only revealed because we knew the experimentally determined outcome. A challenge for occupancy‐detection models is to find ways to identify and mitigate the impacts of unobserved heterogeneity, which could unknowingly bias many models. 相似文献
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Lennis Beatriz Ordua-Castillo Jorge Eduardo del-Río-Robles Irving García-Jimnez Csar Zavala-Barrera Yarely Mabell Beltrn-Navarro Joseline Janai Hidalgo-Moyle Iliana Ramírez-Rangel Marco A. Hernndez-Bedolla Alma P. Reyes-Ibarra Margarita Valadez-Snchez Jos Vzquez-Prado Guadalupe Reyes-Cruz 《Journal of cell communication and signaling》2022,16(2):239
Calcium sensing receptor, a pleiotropic G protein coupled receptor, activates secretory pathways in cancer cells and putatively exacerbates their metastatic behavior. Here, we show that various CaSR mutants, identified in breast cancer patients, differ in their ability to stimulate Rac, a small Rho GTPase linked to cytoskeletal reorganization and cell protrusion, but are similarly active on the mitogenic ERK pathway. To investigate how CaSR activates Rac and drives cell migration, we used invasive MDA-MB-231 breast cancer cells. We revealed, by pharmacological and knockdown strategies, that CaSR activates Rac and cell migration via the Gβγ-PI3K-mTORC2 pathway. These findings further support current efforts to validate CaSR as a relevant therapeutic target in metastatic cancer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00662-y. 相似文献
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Christopher Minteer Marco Morselli Margarita Meer Jian Cao Albert HigginsChen Sabine M. Lang Matteo Pellegrini Qin Yan Morgan
E. Levine 《Aging cell》2022,21(2)
Aging is associated with dramatic changes to DNA methylation (DNAm), although the causes and consequences of such alterations are unknown. Our ability to experimentally uncover mechanisms of epigenetic aging will be greatly enhanced by our ability to study and manipulate these changes using in vitro models. However, it remains unclear whether the changes elicited by cells in culture can serve as a model of what is observed in aging tissues in vivo. To test this, we serially passaged mouse embryonic fibroblasts (MEFs) and assessed changes in DNAm at each time point via reduced representation bisulfite sequencing. By developing a measure that tracked cellular aging in vitro, we tested whether it tracked physiological aging in various mouse tissues and whether anti‐aging interventions modulate this measure. Our measure, termed CultureAGE, was shown to strongly increase with age when examined in multiple tissues (liver, lung, kidney, blood, and adipose). As a control, we confirmed that the measure was not a marker of cellular senescence, suggesting that it reflects a distinct yet progressive cellular aging phenomena that can be induced in vitro. Furthermore, we demonstrated slower epigenetic aging in animals undergoing caloric restriction and a resetting of our measure in lung and kidney fibroblasts when re‐programmed to iPSCs. Enrichment and clustering analysis implicated EED and Polycomb group (PcG) factors as potentially important chromatin regulators in translational culture aging phenotypes. Overall, this study supports the concept that physiologically relevant aging changes can be induced in vitro and used to uncover mechanistic insights into epigenetic aging. 相似文献
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Margarita Kirkova Elina Tzvetanova Stefani Vircheva Rositsa Zamfirova Beata Grygier Marta Kubera 《Cell biochemistry and function》2010,28(6):497-502
In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14‐day treatment with fluoxetine (10 mg kg?1 day?1, i.p.), the endogenous antioxidant non‐enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug‐protective effect against the melanoma‐induced oxidative changes (increased LP and decreased total glutathione (GSH)‐level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose‐dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma‐induced oxidative changes in mice spleen. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
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