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71.
Fort DJ Rogers RL McLaughlin DW Sellers CM Schlekat CL 《Biological trace element research》2002,90(1-3):117-142
The toxicity of boron has been understood for many years. However, limited data currently exist concerning the nutritional
essentiality of B in chordates. Results from an ongoing research program evaluating the nutritional essentiality of B in the
South African clawed frog, Xenopus laevis, found that X. laevis fed a low-B diet in a low-B culture media produced a substantially higher number of necrotic eggs and fertilized embryos
than frogs fed a boron-sufficient diet. Markedly decreased embryo cell counts at mid-blastula transition and an increased
frequency of abnormal gastrulation were also noted in embryos from adult frogs fed the B-deficient diet. By 96 h of development,
none of the larvae collected from the B-deficient adults and maintained in low-boron culture media developed normally. Reproductive
effects associated with B deficiency in female Xenopus included ovary atrophy, oocyte necrosis, and incomplete oocyte maturation. In males, a decrease in testis weight and sperm
count was noted. These studies suggest that these adverse effects resulting from B deficiency could be found during gametogenesis,
gamete maturation embryonic development, and larval maturation. The studies also confirmed that B deficiency was capable of
interrupting the X. laevis life cycle. Additional studies evaluating the role of B in the thyroid axis and the oocyte plasma membrane progesterone receptor
provide the first line of direct evidence for a biochemical role of boron in X. laevis. Combined together, this research program provides firm evidence that B is nutritionally essential in X. laevis. 相似文献
72.
Fort DJ 《Biological trace element research》2002,85(2):157-169
Processes of oocyte maturation that may be affected by boron (B) deficiency were studied to potentially determine a possible
biochemical role of B in the Xenopus laevis oocyte. More specifically, the Xenopus oocyte membrane progesterone receptor (OMPR) in B-deficient oocytes was characterized by evaluating progesterone affinity
for the OMPR and OMPR responsiveness to progesterone stimulation. The responsiveness of B-deficient oocytes to microinjection
of a purified oocyte cytoplasmic fraction (OCF) from B-adequate oocytes was also studied to evaluate which aspects of the
maturation process were affected by B deficiency. Results suggested that B deficiency resulted in incomplete oocyte maturation
and that maturation could not be induced by the administration of exogenous progesterone. Progesterone successfully induced
germinal vesicle breakdown (GVBD) in oocytes from females fed a B-supplemented diet (+B) and females administered a traditional
diet of beef liver and lung (B adequate). Addition of exogenous B to the -B oocytes increased the rate of progesterone-induced
GVBD slightly. The B-deficient X. laevis oocytes were capable of undergoing GVBD when endogenously stimulated by microinjected purified B-adequate OCF. These results
indicated that the inability of the B-deficient oocytes to undergo GVBD was not associated with the cytoplasmic induction
process specifically, but possibly in the progesterone receptor or signal transduction pathways. Radio-binding studies found
that progesterone binding to the B-deficient OPMR was greatly reduced compared to B-adequate or B-supplemented OMPR. Moreover,
washout studies determined that progesterone binding to the OMPR in B-deficient oocytes was more transient than the B adequate
or +B oocytes. 相似文献
73.
Fort DJ Propst TL Stover EL Strong PL Murray FJ 《Biological trace element research》1998,66(1-3):237-259
Frog embryo teratogenesis assay—Xenopus (FETAX) was utilized as a model system to evaluate the effects on embryo-larval development at various low boron (B) exposure
levels in the culture media. Concentrations tested ranged from <1 to 5000 μg B/L. A statistically significant (P < 0.05) increase
in malformations was observed at ≤ 3 μg B/L, but not at the greater concentrations. Abnormal development of the gut, craniofacial
region and eye, visceral edema, and kinking of the tail musculature (abnormal myotome development) and notochord were observed.
In subsequent studies, adult frogs were maintained for 28 d on two diets: (1) low B (LB, 62 μg B/kg) or (2) boric acid supplemented
(BA, 1851 μg B/kg); the frogs were subsequently mated, and their offspring were cultured in media containing various levels
of B. Results of the 28-d depletion studies indicated that frogs maintained under LB conditions produced a greater proportion
of (1) necrotic eggs and (2) fertilized embryos, which abnormally gastrulated at a greater rate and were substantially less
viable than embryos from frogs fed the BA diet. Malformations similar to those seen in the initial study were observed in
embryos from the B-depleted adults maintained in an LB environment; 28 d on the LB diet enhanced the incidence of malformations
associated with the LB culture media. These abnormalities were not observed in embryos cultured in ≥4 μg B/L from adults cultured
on the BA diet. These studies showed that insufficient B reproducibly interfered with normalXenopus laevis development during organogenesis, substantially impaired normal reproductive function in adult frogs, and thus represent
the first studies demonstrating the nutritional essentiality of B in an amphibian species. 相似文献
74.
Drosophila melanogaster stock consisting of meiotic recombination deficient (Rec−) double mutant mei-9a mei-41D5 males and Rec+ females was exposed at the larval stage to an aromatic amine or a polycyclic aromatic hydrocarbon. After emergence as adult flies, the males and the females were scored separately. When the treatment caused a dose-dependent reduction in the male to female ratio from the control level, the experiment was repeated with a larval stock consisting of Rec+ males and Rec+ females under comparable conditions. A preferential killing effect upon Rec− larvae was taken as evidence of DNA damaging effect of the test compound. Among 16 compounds tested, 1-AP, B(a)P, 2-AF, DAF, 4-AAF, 2-AAF, 1-AA, 2-AA, DMA, B(a)A and DMBA were registered as positive; Py and 3-MC were weakly positive; and B(e)P, Fluo and Ant were negative. The selective killing effects of the compounds in each of the pyrene, fluorene and anthracene series varied drastically as a function of structure in a way similar to that reported for the genotoxicity in Drosophila and the carcinogenicity in rodents. The Drosophila DNA repair assay will serve as a simple adjunct to the already available means for studying the genotoxic potency of aromatic amines and polycyclic aromatic hydrocarbons. 相似文献
75.
Causeret F Hidalgo-Sanchez M Fort P Backer S Popoff MR Gauthier-Rouvière C Bloch-Gallego E 《Development (Cambridge, England)》2004,131(12):2841-2852
During embryonic development, tangentially migrating precerebellar neurons emit a leading process and then translocate their nuclei inside it (nucleokinesis). Netrin 1 (also known as netrin-1) acts as a chemoattractant factor for neurophilic migration of precerebellar neurons (PCN) both in vivo and in vitro. In the present work, we analyzed Rho GTPases that could direct axon outgrowth and/or nuclear migration. We show that the expression pattern of Rho GTPases in developing PCN is consistent with their involvement in the migration of PCN from the rhombic lips. We report that pharmacological inhibition of Rho enhances axon outgrowth of PCN and prevents nuclei migration toward a netrin 1 source, whereas inhibition of Rac and Cdc42 sub-families impair neurite outgrowth of PCN without affecting migration. We show, through pharmacological inhibition, that Rho signaling directs neurophilic migration through Rock activation. Altogether, our results indicate that Rho/Rock acts on signaling pathways favoring nuclear translocation during tangential migration of PCN. Thus, axon extension and nuclear migration of PCN in response to netrin 1 are not strictly dependent processes because: (1) distinct small GTPases are involved; (2) axon extension can occur when migration is blocked; and (3) migration can occur when axon outgrowth is impaired. 相似文献
76.
Insecticide resistance: a silent base prediction 总被引:3,自引:0,他引:3
Weill M Berthomieu A Berticat C Lutfalla G Nègre V Pasteur N Philips A Leonetti JP Fort P Raymond M 《Current biology : CB》2004,14(14):R552-R553
77.
78.
Characterization of the heparin-binding site of the mycobacterial heparin-binding hemagglutinin adhesin 总被引:10,自引:0,他引:10
Pethe K Aumercier M Fort E Gatot C Locht C Menozzi FD 《The Journal of biological chemistry》2000,275(19):14273-14280
The mycobacterial adhesin heparin-binding hemagglutinin (HBHA) contains several lysine-rich repeats at its carboxyl-terminal end. Using truncated recombinant HBHA forms and hybrid proteins containing HBHA repeats grafted onto the Escherichia coli maltose-binding protein (MBP), we found that these repeats are responsible for heparin binding. Immunofluorescence microscopy studies revealed that their deletion abrogates binding of HBHA to human pneumocytes. Conversely, when fused to MBP, the HBHA repeats confer pneumocyte adherence properties to the hybrid protein. Treatment of pneumocytes with glycosaminoglycan-degrading enzymes showed that HBHA binding depends on the presence of heparan sulfate chains on the cell surface. The epitope of a monoclonal antibody that inhibits mycobacterial adherence to epithelial cells was mapped within the lysine-rich repeats, confirming their involvement in mycobacterial adherence to epithelial cells. Surface plasmon resonance analyses showed that recombinant HBHA binds to immobilized heparin with fast association kinetics (k(a) = 5.62 (+/- 0.10) x 10(5) m(-1) s(-1)), whereas the dissociation kinetics were slower (k(d) = 0.015 (+/- 0.002) s(-1)), yielding a K(D) value of 26 nm. Similar analyses with grafted MBP indicated similar kinetic constants, indicating that the carboxyl-terminal repeats contain the entire heparin-binding site of HBHA. The molecular characterization of the interactions of HBHA with epithelial glycosaminoglycans should help to better understand mycobacterial adherence within the lungs and may ultimately lead to new approaches for therapy or immunoprophylaxis. 相似文献
79.
Suzuki Y Sher A Yap G Park D Neyer LE Liesenfeld O Fort M Kang H Gufwoli E 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(10):5375-5382
The role for IL-10 in the immunopathogenesis of acute toxoplasmosis following peroral infection was examined in both genetically susceptible C57BL/6 and resistant BALB/c mice. C57BL/6-background IL-10-targeted mutant (IL-10-/-) mice all died in 2 wk after infection with 20 cysts of the ME49 strain, whereas only 20% of control mice succumbed. Histological studies revealed necrosis in the small and large intestines and livers of infected IL-10-/- mice. The necrosis in the small intestine was the most severe pathologic response and was not observed in control mice. Treatment of infected IL-10-/- mice with either anti-CD4 or anti-IFN-gamma mAb prevented intestinal pathology and significantly prolonged time to death. Treatment of these animals with anti-IL-12 mAb also prevented the pathology. Significantly greater amounts of IFN-gamma mRNA were detected in the lamina propria lymphocytes obtained from the small intestine of infected IL-10-/- mice than those from infected control mice. In common with C57BL/6-background IL-10-/- mice, BALB/c-background IL-10-/- mice all died developing intestinal pathology after infection. Control BALB/c mice all survived even after infection with 100 cysts and did not develop the intestinal lesions. Treatment with anti-IFN-gamma mAb prevented the pathology and prolonged time to death of the infected IL-10-/- mice. These results strongly suggest that IL-10 plays a critical role in down-regulating IFN-gamma production in the small intestine following sublethal peroral infection with Toxoplasma gondii and that this down-regulatory effect of IL-10 is required for prevention of development of IFN-gamma-mediated intestinal pathology and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice. 相似文献
80.
Selectively functionalized 2,5-imino-D-glucitol and 1,5-imino-D-mannitol derivatives were synthesized and tested as precursors of hydrolytically resistant pseudo-disaccharides. Among them N-acetyl-6-amino-6-deoxy-2,5-imino-D-glucitol (11) and N-acetyl-6-amino-6-deoxy-1,5-imino-D-mannitol (12) were found potent and specific inhibitors against beta-D-glucosidase and alpha-L-fucosidase, respectively. 相似文献