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排序方式: 共有96条查询结果,搜索用时 15 毫秒
31.
Challet C Maechler P Wollheim CB Ruegg UT 《The Journal of biological chemistry》2001,276(6):3791-3797
Mitochondrial Ca(2+) concentration ([Ca(2+)](m)) was monitored in C2C12 skeletal muscle cells stably expressing the Ca(2+)-sensitive photoprotein aequorin targeted to mitochondria. In myotubes, KCl-induced depolarization caused a peak of 3.03 +/- 0.14 micrometer [Ca(2+)](m) followed by an oscillatory second phase (5.1 +/- 0.1 per min). Chelation of extracellular Ca(2+) or blockade of the voltage-operated Ca(2+) channel attenuated both phases of the KCl response. The inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, cyclopiazonic acid, reduced the amplitude of the KCl-induced [Ca(2+)](m) peak and prevented the oscillations, suggesting that these were generated intracellularly. No such [Ca(2+)](m) oscillations occurred with the nicotinic agonist carbachol, cyclopiazonic acid alone, or the purinergic agonist ATP. In contrast, caffeine produced an oscillatory behavior, indicating a role of ryanodine receptors as mediators of the oscillations. The [Ca(2+)](m) response was desensitized when cells were exposed to two consecutive challenges with KCl separated by a 5-min wash, whereas a second pulse of carbachol potentiated [Ca(2+)](m), indicating differences in intracellular Ca(2+) redistribution. Cross-desensitization between KCl and carbachol and cross-potentiation between carbachol and KCl were observed. These results suggest that close contacts between mitochondria and sarcoplasmic reticulum exist permitting Ca(2+) exchanges during KCl depolarization. These newly demonstrated dynamic changes in [Ca(2+)](m) in stimulated skeletal muscle cells might contribute to the understanding of physiological and pathological processes in muscular disorders. 相似文献
32.
33.
Kristen Ruegg Eric C. Anderson Jason Boone Jazz Pouls Thomas B. Smith 《Molecular ecology》2014,23(19):4757-4769
Next‐generation sequencing has made it possible to begin asking questions about the process of divergence at the level of the genome. For example, recently, there has been a debate around the role of ‘genomic islands of divergence’ (i.e. blocks of outlier loci) in facilitating the process of speciation‐with‐gene‐flow. The Swainson's thrush, Catharus ustulatus, is a migratory songbird with two genetically distinct subspecies that differ in a number of traits known to be involved in reproductive isolation in birds (plumage coloration, song and migratory behaviour), despite contemporary gene flow along a secondary contact zone. Here, we use RAD‐PE sequencing to test emerging hypotheses about the process of divergence at the level of the genome and identify genes and gene regions involved in differentiation in this migratory songbird. Our analyses revealed distinct genomic islands on 15 of the 23 chromosomes and an accelerated rate of divergence on the Z chromosome, one of the avian sex chromosomes. Further, an analysis of loci linked to traits known to be involved in reproductive isolation in songbirds showed that genes linked to migration are significantly more differentiated than expected by chance, but that these genes lie primarily outside the genomic islands. Overall, our analysis supports the idea that genes linked to migration play an important role in divergence in migratory songbirds, but we find no compelling evidence that the observed genomic islands are facilitating adaptive divergence in migratory behaviour. 相似文献
34.
Naoki Ito Urs T. Ruegg Akira Kudo Yuko Miyagoe-Suzuki Shin’ichi Takeda 《Channels (Austin, Tex.)》2013,7(3):221-224
Mechanical load-induced intracellular signaling events are important for subsequent skeletal muscle hypertrophy. We previously showed that load-induced activation of the cation channel TRPV1 caused an increase in intracellular calcium concentrations ([Ca2+]i) and that this activated mammalian target of rapamycin (mTOR) and promoted muscle hypertrophy. However, the link between mechanical load-induced intracellular signaling events, and the TRPV1-mediated increases in [Ca2+]i are not fully understood. Here we show that administration of the TRPV1 agonist, capsaicin, induces phosphorylation of mTOR, p70S6K, S6, Erk1/2 and p38 MAPK, but not Akt, AMPK or GSK3β. Furthermore, the TRPV1-induced phosphorylation patterns resembled those induced by mechanical load. Our results continue to highlight the importance of TRPV1-mediated calcium signaling in load-induced intracellular signaling pathways. 相似文献
35.
Colin W. Rundel Michael B. Wunder Allison H. Alvarado Kristen C. Ruegg Ryan Harrigan Andrew Schuh Jeffrey F. Kelly Rodney B. Siegel David F. DeSante Thomas B. Smith John Novembre 《Molecular ecology》2013,22(16):4163-4176
Methods for determining patterns of migratory connectivity in animal ecology have historically been limited due to logistical challenges. Recent progress in studying migratory bird connectivity has been made using genetic and stable‐isotope markers to assign migratory individuals to their breeding grounds. Here, we present a novel Bayesian approach to jointly leverage genetic and isotopic markers and we test its utility on two migratory passerine bird species. Our approach represents a principled model‐based combination of genetic and isotope data from samples collected on the breeding grounds and is able to achieve levels of assignment accuracy that exceed those of either method alone. When applied at large scale the method can reveal specific migratory connectivity patterns. In Wilson's warblers (Wilsonia pusilla), we detect a subgroup of birds wintering in Baja that uniquely migrate preferentially from the coastal Pacific Northwest. Our approach is implemented in a way that is easily extended to accommodate additional sources of information (e.g. bi‐allelic markers, species distribution models, etc.) or adapted to other species or assignment problems. 相似文献
36.
P. V. Avdonin K. V. Surkov I. F. Sukhanova U. T. Ruegg 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2008,2(4):365-371
Expression of channel protein Orai-1 has been demonstrated in cultured skeletal myoblasts and myotubes. In order to evaluate its functional role in Ca2+ transport in these cells we used small interfering RNA (siRNA) targeted against mRNA coding for Orai-1. Optimal conditions for the effective transfection of myoblasts and myotubes were found. In experiments using myotubes from an mdx cell line we have shown that inactivation of mRNA coding Orai-1 results in complete suppression of 45Ca2+ entry induced by thapsigargin, an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase. The data obtained indicate that Orai-1 is involved in store-activated Ca2+ entry into skeletal myotubes. 相似文献
37.
L Fong D Brockstedt C Benike J K Breen G Strang C L Ruegg E G Engleman 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(12):7150-7156
Many tumor-associated Ags represent tissue differentiation Ags that are poorly immunogenic. Their weak immunogenicity may be due to immune tolerance to self-Ags. Prostatic acid phosphatase (PAP) is just such an Ag that is expressed by both normal and malignant prostate tissue. We have previously demonstrated that PAP can be immunogenic in a rodent model. However, generation of prostate-specific autoimmunity was seen only when a xenogeneic homolog of PAP was used as the immunogen. To explore the potential role of xenoantigen immunization in cancer patients, we performed a phase I clinical trial using dendritic cells pulsed with recombinant mouse PAP as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly vaccinations of xenoantigen-loaded dendritic cells with minimal treatment-associated side effects. All patients developed T cell immunity to mouse PAP following immunization. Eleven of the 21 patients also developed T cell proliferative responses to the homologous self-Ag. These responses were associated with Ag-specific IFN-gamma and/or TNF-alpha secretion, but not IL-4, consistent with induction of Th1 immunity. Finally, 6 of 21 patients had clinical stabilization of their previously progressing prostate cancer. All six of these patients developed T cell immunity to human PAP following vaccination. These results demonstrate that xenoantigen immunization can break tolerance to a self-Ag in humans, resulting in a clinically significant antitumor effect. 相似文献
38.
B A Myers M P Lawton C L Ruegg M L Bruss C E Cornelius 《The International journal of biochemistry》1990,22(1):61-65
1. Bolivian squirrel monkeys (BoSMs), which are animal models for Gilbert's syndrome, have 40% less hepatic bilirubin UDP-glucuronyltransferase (BR-UPPG-T) activity than Brazilian squirrel monkeys (BrSMs). 2. Although fasting results in similar decreases in hepatic UDP-glucose and UDP-glucuronate levels in both simian subspecies, increased activities (55%) of BR-UDPG-T are induced only in the fasted control BrSMs, which do not exhibit the marked fasting hyperbilirubinemia (FH). 3. Total hepatic bilirubin (BR) concentrations were 50% greater in both fed and fasted BoSMs when compared to BrSMs. 4. Hepatic unconjugated BR levels increase upon fasting only in Gilbert-like BoSMs, reaching concentrations twice that observed in BrSMs. 5. Elevated hepatic BR levels in fasted BoSMs may reflect BR overproduction or inadequate glucuronidation. 6. The increased BR-UDPG-T activity induced in BrSMs during fasting could compensate in-part for the UDPGA depletion and prevent the marked FH as observed in BoSMs. 相似文献
39.
Kristen C. Ruegg Eric C. Anderson Kristina L. Paxton Vanessa Apkenas Sirena Lao Rodney B. Siegel David F. DeSante Frank Moore Thomas B. Smith 《Molecular ecology》2014,23(23):5726-5739
Neotropic migratory birds are declining across the Western Hemisphere, but conservation efforts have been hampered by the inability to assess where migrants are most limited—the breeding grounds, migratory stopover sites or wintering areas. A major challenge has been the lack of an efficient, reliable and broadly applicable method for measuring the strength of migratory connections between populations across the annual cycle. Here, we show how high‐resolution genetic markers can be used to identify genetically distinct groups of a migratory bird, the Wilson's warbler (Cardellina pusilla), at fine enough spatial scales to facilitate assessing regional drivers of demographic trends. By screening 1626 samples using 96 highly divergent single nucleotide polymorphisms selected from a large pool of candidates (~450 000), we identify novel region‐specific migratory routes and timetables of migration along the Pacific Flyway. Our results illustrate that high‐resolution genetic markers are more reliable, precise and amenable to high throughput screening than previously described intrinsic marking techniques, making them broadly applicable to large‐scale monitoring and conservation of migratory organisms. 相似文献
40.
Rachel Miloslavski ;Elad Cohen ;Adam Avraham ;Yifat I luz ;Zvi Hayouka ;Judith Kasir ;Rajini Mudhasani ;Stephen N. Jones ;Nadine Cybulski ;Markus A. Ruegg ;Ola Larsson ;Valentina Gandin ;Arjuna Rajakumar ;Ivan Topisirovic ;Oded Meyuhas 《分子细胞生物学报》2014,(3):255-266
Cells encountering hypoxic stress conserve resources and energy by downregulating the protein synthesis. Here we demonstrate that one mechanism in this response is the translational repression of TOP mRNAs that encode components of the translational apparatus. This mode of regulation involves TSC and Rheb, as knockout of TSC1 or TSC2 or overexpression of Rheb rescued TOP mRNA translation in oxygen-deprived celts. Stress-induced translational repression of these mRNAs closely correlates with the hypophosphorylated state of 4E-BP, a translational repressor. However, a series of 4E-BP loss- and gain-of-function experiments disprove a cause-and- effect relationship between the phosphorylation status of 4E-BP and the translational repression of TOP mRNAs under oxygen or growth factor deprivation. Furthermore, the repressive effect of anoxia is similar to that attained by the very efficient inhibition of mTOR activity by Torin 1, but much more pronounced than roptor or rictor knockouL Likewise, deficiency of raptor or rictor, even though it mildly downregulated basal translation efficiency of TOP mRNAs, failed to suppress the oxygen-mediated translational activation of TOP mRNAs. Finally, co-knockdown of TIA-1 and TIAR, two RNA-binding proteins previously implicated in translational repression of TOP mRNAs in amino acid-starved cells, failed to relieve TOP mRNA translation under other stress conditions. Thus, the nature of the proximal translational regulator of TOP m RNAs remains elusive. 相似文献