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71.
72.
There is a large body of evidence supporting a role for GTP-binding proteins in signal transduction by growth factors. In certain cells, ligands which activate or inhibit the production of cAMP via heterotrimeric G proteins promote replication of the target cell. These mechanisms play an important role in a limited number of tumours. Ligands which activate PI hydrolysis through heterotrimeric G proteins may also promote growth in certain systems, but the precise role for PI hydrolysis remains to be determined. Receptors with intrinsic tyrosine kinases may also interact with the heterotrimeric G proteins, but it is not known if these interactions represent side reactions, or whether they are central in the responses of certain cell types. Lastly, p21ras and other small molecular weight G proteins appear to be profoundly important in growth control. The tyrosine kinase growth factor receptors may interact indirectly with these GTP binding proteins via GAP proteins. The molecular detail of this process is emerging rapidly and is likely to be worked out in the near future. 相似文献
73.
Human neutrophils contain subpopulations of specific granules exhibiting different sensitivities to changes in cytosolic free calcium 总被引:3,自引:0,他引:3
H D Perez S Marder F Elfman H E Ives 《Biochemical and biophysical research communications》1987,145(2):976-981
We examined the role of mobilization of intracellular calcium in the ability of human neutrophils to discharge specific granule constituents upon stimulation with the synthetic chemotactic factor, N-formyl-met-leu-phe. Extracellular calcium was not required for optimal secretion of the specific granule markers lactoferrin and vitamin B12-binding protein. Depletion and chelation of intracellular calcium, as well as reconstitution experiments, however, revealed different calcium requirements for stimulated secretion of these markers. N-formyl-met-leu-phe-induced secretion of vitamin B12-binding protein required half-maximal change in intracellular calcium of greater than 20 nM, while lactoferrin requirements were approximately 140 nM. Thus, it appears that cytosolic free calcium modulates fusion of subpopulations of specific granules which with the neutrophil plasma membrane. 相似文献
74.
V K Jenkins S C Barranco C M Townsend R R Perry K L Ives 《International journal of radiation biology and related studies in physics, chemistry, and medicine》1986,50(2):269-278
In vitro effects of radiation were studied in two permanent cell lines (AGS and SII) from two patients with adenocarcinoma of the stomach and three permanent sublines from each cell line. Radiation survival parameters for AGS and SII parent cell lines and sublines were determined after in vitro irradiation of their cells with 0.5 to 10 Gy of 60Co gamma rays. The AGS and SII cell lines had different growth properties, DNA contents and radiation survival curves. Surviving fractions of SII parent cells (76 chromosomes) after 2.0 and 10 Gy were 1.22 and 17.8 times greater, respectively, than values for AGS parent cells (47 chromosomes). Sensitivities (D0) were 1.08 and 1.45 Gy for AGS and SII parent lines, respectively. The D0 values for AGS parent cells and sublines were similar (1.01 to 1.08 Gy), but SII parent cells and sublines had D0 values of 1.45, 1.36, 1.37 and 1.12 Gy (for SII-A). Also, the SII parent cells had survival fractions after 2.0 and 10 Gy that were 1.3 and 11.3 times greater, respectively, than values for the SII-A cells. These data show differences in radiation responses among stomach cancer cell lines and sublines that may relate to DNA content, but there was no consistent correlation between radiation response and a particular cell characteristic. 相似文献
75.
Simon Mays Rachel Ives Megan Brickley 《American journal of physical anthropology》2009,140(3):410-416
Endochondral growth, appositional growth, and acquisition of cortical bone thickness in the femur are investigated in subadult skeletons (N = 43, dental age range birth to 12 years) from the 19th‐century AD burial site of St. Martin's churchyard, Birmingham, England. Endochondral growth is monitored using diaphyseal femoral length. Appositional growth is monitored using radiographic midshaft mediolateral width and acquisition of cortical bone using combined mediolateral cortical thickness measured at the midshaft from radiographs. The methodology involves plotting these variables against dental age. Growth is compared in children of differing socioeconomic status. Higher and lower status individuals are identified in the assemblage by their burial in brick vaults in the case of the former and in earth‐cut graves in the case of the latter. The relationships between bone dimensions and dental age are described using a polynomial regression procedure, and analysis of regression residuals is used to evaluate differences in bone dimension‐for‐dental age between the two status groups. Results show that lower socioeconomic status individuals had lower cortical thickness‐for‐dental age than those of higher status. This was interpreted as likely reflecting poorer nutrition in the children of lower socioeconomic backgrounds. There was no patterning with respect to socioeconomic status in femur diaphyseal length or midshaft width. The results support the idea that, for skeletal populations, growth in cortical thickness may be a more sensitive indicator of adverse conditions in childhood than growth in bone length or width. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
76.
A K El-Fadili H Zangger C Desponds I J Gonzalez H Zalila C Schaff A Ives S Masina J C Mottram N Fasel 《Cell death & disease》2010,1(9):e71
In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H2O2), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes. 相似文献
77.
Individual variation in seed size and seed production is high in many plant species. How does this variation affect seed-dispersing animals and, in turn, the fitness of individual plants? In this study, we first surveyed intraspecific variation in seed mass and production in a population of a Chinese white pine, Pinus armandii. For 134 target trees investigated in 2012, there was very high variation in seed size, with mean seed mass varying among trees almost tenfold, from 0.038 to 0.361 g. Furthermore, 30 of the 134 trees produced seeds 2 years later, and for these individuals there was a correlation in seed mass of 0.59 between years, implying consistent differences among individuals. For a subset of 67 trees, we monitored the foraging preferences of scatter-hoarding rodents on a total of 15,301 seeds: 8380 were ignored, 3184 were eaten in situ, 2651 were eaten after being cached, and 395 were successfully dispersed (cached and left intact). At the scale of individual seeds, seed mass affected almost every decision that rodents made to eat, remove, and cache individual seeds. At the level of individual trees, larger seeds had increased probabilities of both predation and successful dispersal: the effects of mean seed size on costs (predation) and benefits (caching) balanced out. Thus, despite seed size affecting rodent decisions, variation among trees in dispersal success associated with mean seed size was small once seeds were harvested. This might explain, at least in part, the maintenance of high variation in mean seed mass among tree individuals. 相似文献
78.
Ives JC Shelley GA 《Journal of strength and conditioning research / National Strength & Conditioning Association》2003,17(1):177-186
Functional training is considered to be training that attempts to mimic the specific physiological demands of real-life activities. Most approaches to functional training, though, omit important factors that contribute to physiological and neuromotor adaptations. Cognitive factors related to sports influence physiological performance, and subsequently, physiological and neuromotor adaptations. We present a rationale and a theoretical framework by which to create effective functional training methods that incorporate cognitive factors. This framework draws upon recent developments and strong empirical evidence in the areas of dynamic systems theory, perceptual skills training, and motor learning/control. Emphasized within rigorous physical training are practice-related techniques and motor-learning strategies. In particular, mental effort, attention, and intention manipulated in a discovery-learning paradigm provide a framework for functional strength and power training. This framework is suggested to help maximize sport-specific physiological adaptations, and subsequently, sports performance. 相似文献
79.
80.
S Hoare J A Copland Z Strakova K Ives Y J Jeng M R Hellmich M S Soloff 《The Journal of biological chemistry》1999,274(40):28682-28689
As the oxytocin receptor plays a key role in parturition and lactation, there is considerable interest in defining its structure/functional relationships. We previously showed that the rat oxytocin receptor transfected into Chinese hamster ovary cells was coupled to both G(q/11) and G(i/o), and that oxytocin stimulated ERK-2 phosphorylation and prostaglandin E(2) synthesis via protein kinase C activity. In this study, we show that deletion of 51 amino acid residues from the carboxyl terminus resulted in reduced affinity for oxytocin and a corresponding rightward shift in the dose-response curve for oxytocin-stimulated [Ca(2+)](i). However, oxytocin-stimulated ERK-2 phosphorylation and prostaglandin E(2) synthesis did not occur in cells expressing the truncated receptor. Oxytocin also failed to increase phospholipase A activity or activate protein kinase C, indicating that the mutant receptor is uncoupled from G(q)-mediated pathways. The Delta51 receptor is coupled to G(i), as oxytocin-stimulated Ca(2+) transients were inhibited by pertussis toxin, and a Gbetagamma sequestrant. Preincubation of Delta51 cells with the tyrosine kinase inhibitor, genistein, also blocked the oxytocin effect. A Delta39 mutant had all the activities of the wild type oxytocin receptor. These results show that the portion between 39 and 51 residues from the COOH terminus of the rat oxytocin receptor is required for interaction with G(q/11), but not G(i/o). Furthermore, an increase in intracellular calcium was generated via a G(i)betagamma-tyrosine kinase pathway from intracellular stores that are distinct from G(q)-mediated inositol trisphosphate-regulated stores. 相似文献