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Isoflavene–propranolol hybrid molecules were developed as potentially novel anti-tumour agents. Isoflavene itself has potent anti-cancer activity while propranolol can enhance anti-proliferative and anti-angiogenic properties of 5-fluorouracil and paclitaxel. The hybrids were produced via nucleophilic addition of substituted amine groups to a dioxiran intermediate, which was in turn generated from the Williamson-type reaction of isoflavene with (±)-epichlorohydrin. These analogues were tested in anti-cancer cell viability assays against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines, and were found to exhibit potent anti-proliferative activities. These compounds also displayed anti-angiogenic and anti-proliferative effects in HMEC-1 human microvascular endothelial cell lines. Notably, the most potent hybrid molecules synthesized in this work showed enhanced potency against cancer cell lines compared to either isoflavene or propranolol alone, while retaining significant selectivity for cancer cells over MRC-5 normal lung fibroblast cells.  相似文献   
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Kasey E. Barton 《Oikos》2008,117(6):917-925
Phenotypic plasticity in growth (leading to compensation) and secondary chemical production (leading to induction) in response to herbivory are key defense strategies in adult plants, but their role in seedling defense remains unclear. A pair of greenhouse studies was conducted to investigate compensation and induction in seedlings and juvenile plants, using Plantago lanceolata (Plantaginaceae) and the specialist buckeye caterpillar Junonia coenia (Nymphalidae) as a model system. Plants received 50% defoliation at two and four weeks of age, and groups of plants were harvested one week after herbivory and six to eight weeks after herbivory to investigate the duration of the responses. Plants damaged at two weeks showed no chemical induction and fully compensated for the lost leaf tissue by ten weeks of age. Plants damaged at four weeks showed a significant reduction in iridoid glycosides one week after herbivory and achieved full shoot compensation by ten weeks of age at the expense of root biomass. These results indicate that P. lanceolata seedlings use compensation, but not chemical induction, as a defense strategy. This research highlights the importance of considering ontogeny in studies of plant–herbivore interactions and suggests that seedling defense may differ markedly from adult plant defense.  相似文献   
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ABSTRACT

Background

Climates are changing at a rate that exceeds the adaptive capacity of species, especially endangered species. Genetic variation and phenotypic plasticity are important for population persistence, yet few studies have linked traits to seedling performance under drought in endangered species.  相似文献   
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Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients. Clinical trials, while promising, have been difficult to activate and accrue. While individual institutions and investigators have attempted to seek solutions to such problems, international, national, and local partnership may provide the keys to more efficient and innovative paths forward. Furthermore, a mucosal melanoma coalition would provide a potential network for patients and caregivers to seek expert opinion and advice. The Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA) highlighted the current clinical challenges faced by patients, providers, and scientists, identified current and future clinical trial investigations in this rare disease space, and aimed to increase national and international collaboration among the mucosal melanoma community in an effort to improve patient outcomes. The included proceedings highlight the clinical challenges of mucosal melanoma, global clinical trial experience, basic science advances in mucosal melanoma, and future directions, including the creation of shared rare tumor registries and enhanced collaborations.  相似文献   
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Secondary sexual traits are often assumed to increase reproductive success but can also carry costs for males bearing them. Here, we investigate potential foraging costs of foreleg ornamentation in wolf spiders in the genus Schizocosa. Given that the forelegs are involved in securing prey items and that ornaments may also inhibit general mobility, we hypothesized that the presence of ornamentation inhibits foraging success. To test this, we first took an ontogenetic approach. We conducted an experiment to examine variation in foraging behavior before and after ornament development in a population of Schizocosa that exhibits two male phentoypes: (a) brush-legged males that develop large brushes of hairs on their forelegs upon maturation and (b) non-ornamented males that lack ornamentation. When comparing penultimate versus mature foraging behavior between these two phenotypes, we predicted (i) reduced foraging intensity upon maturation for males of both groups (due to increased mate-searching behavior) and (ii) a greater decrease in foraging efficiency in brush-legged versus non-ornamented males (due to costs of ornamentation). As expected, we found that when exposed to prey, all males exhibited greater latencies to attack as matures than as penultimates, but unexpectedly, they differed in their patterns of attack frequency; brush-legged males decreased the number of attacks upon maturation while non-ornamented males increased. We found no support for our second prediction: neither male phenotype exhibited a change in foraging success upon maturation. Given that foraging behavior differed between ontogenetic stages, making it difficult to isolate the effects of ornamentation per se, we conducted a second experiment with a pure brush-legged population (S. ocreata) to directly test the influence of foreleg brushes on foraging behavior. We compared foraging behavior between mature males with brushes present versus mature males with brushes artificially removed and found no effect of the presence/absence of brushes on foraging success. In summary, using both ontogenetic and ornament manipulation approaches, we found no support for the hypothesis that ornamentation influences foraging success; however, we do document phenotype-dependent foraging behavior.  相似文献   
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