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71.
Bevacizumab treatment can result in tumor shrinkage of progressive vestibular schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on meningiomas has not been defined.To determine the clinical activity of bevacizumab against NF2-related meningiomas, we measured changes in volume of meningiomas in NF2 patients who received bevacizumab for treatment of progressive vestibular schwannomas. A radiographic response was defined as a 20% decrease in tumor size by volumetric MRI analysis. In addition, we determined the expression pattern of growth factors associated with tumor angiogenesis in paraffin-embedded tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2 patients were included in this study with a median follow up time of 18 months. A volumetric radiographic response was seen in 29% of the meningiomas (14/48). Tumor shrinkage was not durable: the median duration of response was 3.7 months and the median time to progression was 15 months. There was no significant correlation between pre-treatment growth rate and meningioma response in regression models. Tissue analysis showed no correlation between tumor microvascular density and expression of VEGF pathway components. This data suggests that, in contrast to schwannomas, activation of VEGF pathway is not the primary driver of angiogenesis in meningiomas. Our results suggest that a minority of NF2-associated meningiomas shrink during bevacizumab therapy and that these responses were of short duration. These results are comparable to previous studies of bevacizumab in sporadic meningiomas.  相似文献   
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Background

In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste.

Methods

To investigate how the architecture and composition of the TAS2R14 binding pocket enables specific interactions with a complex array of chemically diverse bitter agonists, we carried out homology modeling and ligand docking experiments, subjected the receptor to point-mutagenesis of binding site residues and performed functional calcium mobilization assays.

Results

In total, 40 point-mutated receptor constructs were generated to investigate the contribution of 19 positions presumably located in the receptor's binding pocket to activation by 7 different TAS2R14 agonists. All investigated positions exhibited moderate to pronounced agonist selectivity.

Conclusions

Since numerous modifications of the TAS2R14 binding pocket resulted in improved responses to individual agonists, we conclude that this bitter taste receptor might represent a suitable template for the engineering of the agonist profile of a chemoreceptive receptor.

General significance

The detailed structure-function analysis of the highly promiscuous and widely expressed TAS2R14 suggests that this receptor must be considered as potentially frequent target for known and novel drugs including undesired off-effects.  相似文献   
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Plant growth-promoting bacteria (PGPB) control the damage to plants from phytopathogens by a number of different mechanisms including: outcompeting the phytopathogen, physical displacement of the phytopathogen, secretion of siderophores to prevent pathogens in the immediate vicinity from proliferating, synthesis of antibiotics, synthesis of a variety of small molecules that can inhibit phytopathogen growth, production of enzymes that inhibit the phytopathogen and stimulation of the systemic resistance of the plant. Biocontrol PGPB may be improved by genetically engineering them to overexpress one or more of these traits so that strains with several different anti-phytopathogen traits which can act synergistically are created. In engineering these strains it is essential to ensure that the normal functioning of the bacterium is not impaired, i.e., that there is no problem with metabolic load.  相似文献   
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This study tries to unveil the contribution of climatic shift in shaping the extreme body size diversity in terrestrial isopods (Oniscidea). Trying to explain size variation at an interspecific level, we test five hypotheses: (1) Bergmann's Rule and the temperature‐size rule postulate large size in cold areas; (2) The metabolic cold adaptation theory postulates small animal sizes in cold environments; (3) The primary productivity hypothesis predicts size increase in resource‐rich areas; (4) The aridity resistance hypothesis predicts large size in arid regions; and (5). The acidosis hypothesis predicts smaller size with decreasing soil pH. Globally, Bergmann's rule and the aridity hypothesis are weakly supported. Among families and genera, results are variable and idiosyncratic. Conglobating species sizes provide weak support for the acidosis hypothesis. Overall, size is strongly affected by familial affiliation. Isopod size evolution seems to be mainly affected by phylogenetically constrained life‐history traits.  相似文献   
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Arbuscular-mycorrhizal (AM) fungi stabilize the soil and enhance plant growth by alleviating nutrient and drought stress. Their contributions to agriculture are well known, but their role in desert ecosystems has received less attention. The AM status of perennial plants in disturbed and undisturbed plots were investigated in the Sonoran Desert near La Paz, Baja California Sur, Mexico to determine if AM fungi contribute to resource-island stability and plant establishment. All perennial plants (46 species) in the study plots were AM, but root colonization varied widely (<10 to> 70%). Roots of plants that established in greatest numbers in plant-free zones (colonizers) of disturbed areas were highly AM. Plants with trace (<10%) root colonization (cacti of the tribe Pachycereae: Pachycereus pringlei, Machaerocereus gummosus, and Lemaireocereus thurberi; and Agave datilyo) established preferentially in association with nurse trees. The pachycereid cacti grew under Prosopis articulata and A. datilyo under Olneya tesota canopies. Of the nine species of trees and arborescent shrubs in the area, the mature (>20 yr) nurse-legumes P. articulata and O. tesota supported the largest number of under-story plants. Younger plants had only occasional associates. AM propagule densities in plant-free areas were lower than under plant canopies (40 vs. 280 propagules/kg soil). Occurrence of soil mounds (islands) under plants owing to soil deposition was related to the nature of the canopies and to the AM status of the roots. Island soils were enmeshed with AM-fungal hyphae, especially in the upper layer (approximately 10 cm). Seedlings of P. pringlei, growing in a screenhouse for six months in soil collected under P. articulata, had a biomass ten times greater than plants growing in bare-area soil. The results are consistent with the proposition that AM fungi contributed to the plant-soil system of our study area by: (1) helping to stabilize windborne soil that settles under dense plant canopies; (2) enhancing the establishment of colonizer plants in bare soils of disturbed areas; and (3) influencing plant associations through differences in the mycotrophic status of the associates.  相似文献   
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The rumen bacterium Ruminococcus albus binds to and degrades crystalline cellulosic substrates via a unique cellulose degradation system. A unique family of carbohydrate-binding modules (CBM37), located at the C terminus of different glycoside hydrolases, appears to be responsible both for anchoring these enzymes to the bacterial cell surface and for substrate binding.  相似文献   
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