全文获取类型
收费全文 | 85篇 |
免费 | 12篇 |
出版年
2021年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 3篇 |
2013年 | 1篇 |
2012年 | 7篇 |
2011年 | 1篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 7篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2005年 | 2篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有97条查询结果,搜索用时 15 毫秒
31.
Wing Leung Geoffrey Neale Fred Behm Rekha Iyengar David Finkelstein Michael B. Kastan Ching-Hon Pui 《Cancer epidemiology》2010,34(3):303-308
Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Methods: Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. Results: In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (αβT cells and CD45RO+/RA? memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (γδT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO?/RA+ naïve T cell and less SjTREC levels in the blood, whereas the Vβ spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole-genome scanning by SNP microarray analysis. Conclusion: ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. 相似文献
32.
ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome 总被引:1,自引:0,他引:1
Schneider JG Finck BN Ren J Standley KN Takagi M Maclean KH Bernal-Mizrachi C Muslin AJ Kastan MB Semenkovich CF 《Cell metabolism》2006,4(5):377-389
Metabolic syndrome is associated with insulin resistance and atherosclerosis. Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, increases insulin resistance, and accelerates atherosclerosis in apoE-/- mice. Transplantation with ATM-/- as compared to ATM+/+ bone marrow increased vascular disease. Jun N-terminal kinase (JNK) activity was increased in ATM-deficient cells. Treatment of ATM+/+apoE-/- mice with low-dose chloroquine, an ATM activator, decreased atherosclerosis. In an ATM-dependent manner, chloroquine decreased macrophage JNK activity, decreased macrophage lipoprotein lipase activity (a proatherogenic consequence of JNK activation), decreased blood pressure, and improved glucose tolerance. Chloroquine also improved metabolic abnormalities in ob/ob and db/db mice. These results suggest that ATM-dependent stress pathways mediate susceptibility to the metabolic syndrome and that chloroquine or related agents promoting ATM activity could modulate insulin resistance and decrease vascular disease. 相似文献
33.
Most estrous cycles in cows consist of 2 or 3 waves of follicular activity. Waves of ovarian follicular development comprise
the growth of dominant follicles some of which become ovulatory and the others are anovulatory. Ovarian follicular activity
in cows during estrous cycle was studied with a special reference to follicular waves and the circulating concentrations of
estradiol and progesterone. Transrectal ultrasound examination was carried out during 14 interovulatory intervals in 7 cows.
Ovarian follicular activity was recorded together with assessment of serum estradiol and progesterone concentrations. Three-wave
versus two-wave interovulatory intervals was observed in 71.4% of cows. The 3-wave interovulatory intervals differed from
2-wave intervals in: 1) earlier emergence of the dominant follicles, 2) longer in length, and 3) shorter interval from emergence
to ovulation. There was a progressive increase in follicular size and estradiol production during growth phase of each wave.
A drop in estradiol concentration was observed during the static phase of dominant anovulatory follicles. The size of the
ovulatory follicle was always greater and produced higher estradiol compared with the anovulatory follicle. In conclusion,
there was a predominance of 3-wave follicular activity that was associated with an increase in length of interovulatory intervals.
A dominant anovulatory follicle during its static phase may initiate the emergence of a subsequent wave. Follicular size and
estradiol concentration may have an important role in controlling follicular development and in determining whether an estrous
cycle will have 2 or 3-waves. 相似文献
34.
The O-antigen chain from the lipopolysaccharide of Helicobacter pylori
strain UA861 was determined to be composed of an elongated type 2 N -
acetyllactosamine backbone,
-[-->3)-beta-D-Gal-(1-->4)-beta-D-GlcNAc-(1- ]n-->, with
approximately half of the GlcNAc units carrying a terminal alpha-d-Glc
residue at the O -6 position. The O-chain of H.pylori UA861 was terminated
by a N -acetyllactosamine [beta-D-Gal-(1-->4)-beta-D- GlcNAc] (LacNAc)
epitope and did not express terminal Lewis X or Lewis Y blood-group
determinants as previously found in other H.pylori strains. The absence of
terminal Lewis X and Lewis Y blood-group epitopes and the replacement of
Fuc by Glc as a side chain in the O- chain of H.pylori UA861 represents yet
another type of lipopolysaccharide structure from H.pylori species. These
structural differences in H.pylori lipopolysaccharide molecules carry
implications with regard to possible different pathogenic events between
strains and respective hosts.
相似文献
35.
DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways. 总被引:33,自引:4,他引:29
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The tumor suppressor protein p53 serves as a critical regulator of a G1 cell cycle checkpoint and of apoptosis following exposure of cells to DNA-damaging agents. The mechanism by which DNA-damaging agents elevate p53 protein levels to trigger G1/S arrest or cell death remains to be elucidated. In fact, whether damage to the DNA template itself participates in transducing the signal leading to p53 induction has not yet been demonstrated. We exposed human cell lines containing wild-type p53 alleles to several different DNA-damaging agents and found that agents which rapidly induce DNA strand breaks, such as ionizing radiation, bleomycin, and DNA topoisomerase-targeted drugs, rapidly triggered p53 protein elevations. In addition, we determined that camptothecin-stimulated trapping of topoisomerase I-DNA complexes was not sufficient to elevate p53 protein levels; rather, replication-associated DNA strand breaks were required. Furthermore, treatment of cells with the antimetabolite N(phosphonoacetyl)-L-aspartate (PALA) did not cause rapid p53 protein increases but resulted in delayed increases in p53 protein levels temporally correlated with the appearance of DNA strand breaks. Finally, we concluded that DNA strand breaks were sufficient for initiating p53-dependent signal transduction after finding that introduction of nucleases into cells by electroporation stimulated rapid p53 protein elevations. While DNA strand breaks appeared to be capable of triggering p53 induction, DNA lesions other than strand breaks did not. Exposure of normal cells and excision repair-deficient xeroderma pigmentosum cells to low doses of UV light, under conditions in which thymine dimers appear but DNA replication-associated strand breaks were prevented, resulted in p53 induction attributable to DNA strand breaks associated with excision repair. Our data indicate that DNA strand breaks are sufficient and probably necessary for p53 induction in cells with wild-type p53 alleles exposed to DNA-damaging agents. 相似文献
36.
The first Australian record of the lily thrips, Liothrips vaneeckei Priesner, is reported from a bulb farm in Warragul South, Victoria. It is an occasional pest of Lilium bulbs, both in the field and in storage, particularly in the USA and several European countries, and is also infrequently found in considerable numbers on the corms of orchids. 相似文献
37.
38.
39.
Two Molecularly Distinct G2/M Checkpoints Are Induced by Ionizing Irradiation 总被引:27,自引:0,他引:27
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Bo Xu Seong-Tae Kim Dae-Sik Lim Michael B. Kastan 《Molecular and cellular biology》2002,22(4):1049-1059
Cell cycle checkpoints are among the multiple mechanisms that eukaryotic cells possess to maintain genomic integrity and minimize tumorigenesis. Ionizing irradiation (IR) induces measurable arrests in the G(1), S, and G(2) phases of the mammalian cell cycle, and the ATM (ataxia telangiectasia mutated) protein plays a role in initiating checkpoint pathways in all three of these cell cycle phases. However, cells lacking ATM function exhibit both a defective G(2) checkpoint and a prolonged G(2) arrest after IR, suggesting the existence of different types of G(2) arrest. Two molecularly distinct G(2)/M checkpoints were identified, and the critical importance of the choice of G(2)/M checkpoint assay was demonstrated. The first of these G(2)/M checkpoints occurs early after IR, is very transient, is ATM dependent and dose independent (between 1 and 10 Gy), and represents the failure of cells which had been in G(2) at the time of irradiation to progress into mitosis. Cell cycle assays that can distinguish mitotic cells from G(2) cells must be used to assess this arrest. In contrast, G(2)/M accumulation, typically assessed by propidium iodide staining, begins to be measurable only several hours after IR, is ATM independent, is dose dependent, and represents the accumulation of cells that had been in earlier phases of the cell cycle at the time of exposure to radiation. G(2)/M accumulation after IR is not affected by the early G(2)/M checkpoint and is enhanced in cells lacking the IR-induced S-phase checkpoint, such as those lacking Nbs1 or Brca1 function, because of a prolonged G(2) arrest of cells that had been in S phase at the time of irradiation. Finally, neither the S-phase checkpoint nor the G(2) checkpoints appear to affect survival following irradiation. Thus, two different G(2) arrest mechanisms are present in mammalian cells, and the type of cell cycle checkpoint assay to be used in experimental investigation must be thoughtfully selected. 相似文献
40.
Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions 总被引:2,自引:0,他引:2
We have determined the nucleotide sequence of a 1,200-base pair (bp)
genomic fragment that includes the kappa-chain constant-region gene (C
kappa) from two species of native Australian rodents, Rattus leucopus
cooktownensis and Rattus colletti. Comparison of these sequences with each
other and with other rodent C kappa genes shows three surprising features.
First, the coding regions are diverging at a rate severalfold higher than
that of the nearby noncoding regions. Second, replacement changes within
the coding region are accumulating at a rate at least as great as that of
silent changes. Third, most of the amino acid replacements are localized in
one region of the C kappa domain--namely, the carboxy-terminal "bends" in
the alpha-carbon backbone. These three features have previously been
described from comparisons of the two allelic forms of C kappa genes in R.
norvegicus. These data imply the existence of considerable evolutionary
constraints on the noncoding regions (based on as yet undetermined
functions) or powerful positive selection to diversify a portion of the
constant-region domain (whose physiological significance is not known).
These surprising features of C kappa evolution appear to be characteristic
only of closely related C kappa genes, since comparison of rodent with
human sequences shows the expected greater conservation of coding regions,
as well as a predominance of silent nucleotide substitutions within the
coding regions.
相似文献