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101.
A long-standing observation in community ecology is that the scaling of species richness, as exemplified by species-area curves, differs on local and regional scales. This decoupling of scales may be largely due to sampling processes (the increasing constraint imposed by sampling fewer individuals at fine scales), as distinct from ecological processes, such as environmental heterogeneity, that operate across scales. Removal of the sampling constraint from fine-scale richness estimates should yield species-area curves that behave like those of the regions in which they are embedded, but an effective method for this removal has not been available. We suggest an approach that incorporates the manner in which small areas accumulate species over time as a way to remove the signature of sampling processes from fine-scale species-area curves. We report for three species-rich grasslands from two continents how local plant species richness is distributed through time at multiple, nested spatial scales, and we ask whether sampling-corrected curves reflect the spatial scaling of richness of each larger floristic province. Our analysis suggests that fine-scale values of richness are highly constrained by sampling processes, but once these constraints are removed, the spatial scaling of species richness is consistent from the scale of individuals to that of an entire province. 相似文献
102.
103.
Timothy J. Opperman John D. Williams Chad Houseweart Rekha G. Panchal Sina Bavari Norton P. Peet Donald T. Moir Terry L. Bowlin 《Bioorganic & medicinal chemistry》2010,18(6):2123-2130
The bis-indoles are a novel class of compounds with potent antibacterial activity against a broad spectrum of Gram-positive and Gram-negative pathogens. The mechanism of action of these compounds has not been clearly defined. To study the mechanism of action of bis-indoles, selections for mutants of Staphylococcus aureus NCTC 8325 with reduced susceptibility to several chemically related bis-indoles were carried out using serial passages in subinhibitory compound concentrations. Resistant mutants were only obtained for one of the four bis-indoles tested (MBX-1090), and these appeared at concentrations up to 16X MIC within 10–12 passages. MBX-1090 resistance mutations produced a truncated open reading frame of mepR (SAOUHSC_00314), a gene encoding a MarR-like repressor. MepR regulates expression of mepA (SAOUHSC_00315), which encodes a member of the Multidrug and Toxic Compound Extrusion (MATE) family of efflux pumps. MBX-1090 resistance was reverted when mepR (wild type) was provided in trans. Microarray experiments and RT-PCR experiments confirmed that over-expression of mepA is required for resistance. Interestingly, MBX-1090 resistant mutants and strains overexpressing mepA from an expression vector did not exhibit cross-resistance to closely related bis-indole compounds. MBX-1090 did not induce expression of mepA, suggesting that this compound does not directly interact with MepR. Conversely, the bis-indoles that were not substrates of MepA strongly induced mepA expression. The results of this study suggest that MepA and MepR exhibit remarkably distinct substrate specificity for closely related bis-indoles. 相似文献
104.
Treatment of patients diagnosed as schizophrenic with antipsychotic drugs (neuroleptics) is known to cause occasional unexplained depletion of white blood cells, especially neutrophil granulocytes. It has been known for many years that neuroleptics can interfere with the mitochondrial respiratory chain in vitro. Because there has been a growing interest recently in mitochondrial targeting of drugs, and since a quantitative structure-activity relationship (QSAR) model that predicts mitochondrial accumulation of neuroleptics has been published, we investigated the effects of neuroleptics on white blood cell mitochondria. Venous blood samples were collected from both patients undergoing treatment with neuroleptics and healthy volunteers. The samples were processed for transmission electron microscopy. The resulting images of white blood cells were analyzed using stereology to compare quantitatively mitochondrial morphology in the patient and control groups. We found that in patients, but not in controls, there was swelling of mitochondria and fragmentation of the mitochondrial cristae. There also were fewer mitochondria in patients than in controls, although due to the swelling of the organelles, the volume density of mitochondria in the two groups was not significantly different. Such changes are typical of a toxic insult. Consequently, it seems plausible that, since schizophrenia is not a disease considered to affect white blood cells per se, these changes probably are due to the medication. 相似文献
105.
Xiaoyan Pan Martin Wilson Carmel McConville Theodoros N. Arvanitis Julian L. Griffin Risto A. Kauppinen Andrew C. Peet 《Metabolomics : Official journal of the Metabolomic Society》2013,9(3):722-729
Increases in 1H nuclear magnetic resonance spectroscopy (NMR) visible lipids are a well-documented sign of treatment response in cancers. Lipids in cytoplasmic lipid droplets (LDs) are the main contributors to the NMR lipid signals. Two human primitive neuroectodermal tumour cell lines with different sensitivities to cisplatin treatment were studied. Increases in NMR visible saturated and unsaturated lipids in cisplatin treated DAOY cells were associated with the accumulation of LDs prior to DNA fragmentation due to apoptosis. An increase in unsaturated fatty acids (UFAs) was detected in isolated LDs from DAOY cells, in contrast to a slight decrease in UFAs in lipid extracts from whole cells. Oleic acid and linoleic acid were identified as the accumulating UFAs in LDs by heteronuclear single quantum coherence spectroscopy (HSQC). 1H NMR lipids in non-responding PFSK-1 cells were unchanged by exposure to 10 μM cisplatin. These findings support the potential of NMR detectable UFAs to serve as a non-invasive marker of tumour cell response to treatment. 相似文献
106.
Christopher F. Butler Caroline Peet Amy E. Mason Michael W. Voice David Leys Andrew W. Munro 《The Journal of biological chemistry》2013,288(35):25387-25399
Cytochrome P450 monooxygenases (P450s) have enormous potential in the production of oxychemicals, due to their unparalleled regio- and stereoselectivity. The Bacillus megaterium P450 BM3 enzyme is a key model system, with several mutants (many distant from the active site) reported to alter substrate selectivity. It has the highest reported monooxygenase activity of the P450 enzymes, and this catalytic efficiency has inspired protein engineering to enable its exploitation for biotechnologically relevant oxidations with structurally diverse substrates. However, a structural rationale is lacking to explain how these mutations have such effects in the absence of direct change to the active site architecture. Here, we provide the first crystal structures of BM3 mutants in complex with a human drug substrate, the proton pump inhibitor omeprazole. Supported by solution data, these structures reveal how mutation alters the conformational landscape and decreases the free energy barrier for transition to the substrate-bound state. Our data point to the importance of such “gatekeeper” mutations in enabling major changes in substrate recognition. We further demonstrate that these mutants catalyze the same 5-hydroxylation reaction as performed by human CYP2C19, the major human omeprazole-metabolizing P450 enzyme. 相似文献
107.
Bing Li Ramdas Pai Daniel Aiello Ming Di Marjorie H. Barnes Norton P. Peet Terry L. Bowlin Donald T. Moir 《Bioorganic & medicinal chemistry letters》2013,23(12):3481-3486
Benzobisthiazole derivatives were identified as novel helicase inhibitors through high throughput screening against purified Staphylococcus aureus (Sa) and Bacillus anthracis (Ba) replicative helicases. Chemical optimization has produced compound 59 with nanomolar potency against the DNA duplex strand unwinding activities of both B. anthracis and S. aureus helicases. Selectivity index (SI = CC50/IC50) values for 59 were greater than 500. Kinetic studies demonstrated that the benzobisthiazole-based bacterial helicase inhibitors act competitively with the DNA substrate. Therefore, benzobisthiazole helicase inhibitors represent a promising new scaffold for evaluation as antibacterial agents. 相似文献
108.
Dean P. Anderson Monica G. Turner Scott M. Pearson Thomas P. Albright Robert K. Peet Ann Wieben 《Biological invasions》2013,15(6):1217-1230
Shade-tolerant non-native invasive plant species may make deep incursions into natural plant communities, but detecting such species is challenging because occurrences are often sparse. We developed Bayesian models of the distribution of Microstegium vimineum in natural plant communities of the southern Blue Ridge Mountains, USA to address three objectives: (1) to assess local and landscape factors that influence the probability of presence of M. vimineum; (2) to quantify the spatial covariance error structure in occurrence that was not accounted for by the environmental variables; and (3) to synthesize our results with previous findings to make inference on the spatial attributes of the invasion process. Natural plant communities surrounded by areas with high human activity and low forest cover were at highest risk of M. vimineum invasion. The probability of M. vimineum presence also increased with increasing native species richness and soil pH, and decreasing basal area of ericaceous shrubs. After accounting for environmental covariates, evaluation of the spatial covariance error structure revealed that M. vimineum is invading the landscape by a hierarchical process. Infrequent long-distance dispersal events result in new nascent sub-populations that then spread via intermediate- and short-distance dispersal, resulting in 3-km spatial aggregation pattern of sub-populations. Containment or minimisation of its impact on native plant communities will be contingent on understanding how M. vimineum can be prevented from colonizing new suitable habitats. The hierarchical invasion process proposed here provides a framework to organise and focus research and management efforts. 相似文献
109.
Naia Morueta‐Holme Brian J. Enquist Brian J. McGill Brad Boyle Peter M. Jørgensen Jeffrey E. Ott Robert K. Peet Irena Šímová Lindsey L. Sloat Barbara Thiers Cyrille Violle Susan K. Wiser Steven Dolins John C. Donoghue II Nathan J. B. Kraft Jim Regetz Mark Schildhauer Nick Spencer Jens‐Christian Svenning 《Ecology letters》2013,16(12):1446-1454
Despite being a fundamental aspect of biodiversity, little is known about what controls species range sizes. This is especially the case for hyperdiverse organisms such as plants. We use the largest botanical data set assembled to date to quantify geographical variation in range size for ~ 85 000 plant species across the New World. We assess prominent hypothesised range‐size controls, finding that plant range sizes are codetermined by habitat area and long‐ and short‐term climate stability. Strong short‐ and long‐term climate instability in large parts of North America, including past glaciations, are associated with broad‐ranged species. In contrast, small habitat areas and a stable climate characterise areas with high concentrations of small‐ranged species in the Andes, Central America and the Brazilian Atlantic Rainforest region. The joint roles of area and climate stability strengthen concerns over the potential effects of future climate change and habitat loss on biodiversity. 相似文献
110.
Smith C Martinez M Peet J Khanna R 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(10):5784-5790
IL-2/anti-IL-2 complex-based therapy has been proposed as a potential adjunct therapeutic tool to enhance in vivo efficacy of T cell-based immunotherapeutic strategies for chronic viral infections and human cancers. In this study, we demonstrate that IL-2 complex therapy can have discerning effects on CD8(+) T cells depending on their stage of differentiation. To delineate the underlying mechanism for these opposing effects on CD8(+) T cells, we examined the effects of IL-2 therapy during early priming, effector, and memory phases of T cell responses generated following immunization with an adenoviral vector encoding multiple EBV CD8(+) epitopes. IL-2 complex treatment during the early priming phase, which coincided with low levels of IL-2Rβ (CD122) and higher levels of IL-2Rα (CD25) on CD8(+) T cells, did not induce the expansion of effector T cells. In contrast, IL-2 complex treatment following the establishment of memory enhanced the expansion of Ag-specific T cells. Additionally, central memory T cells preferentially expanded following treatment at the expense of effector memory T cell populations. These studies demonstrate how differentiation status of the responding CD8(+) T cells impacts on their responsiveness to IL-2 complexes and highlight that timing of treatment should be considered before implementing this therapy in a clinical setting. 相似文献