全文获取类型
收费全文 | 2705篇 |
免费 | 259篇 |
出版年
2022年 | 26篇 |
2021年 | 48篇 |
2020年 | 22篇 |
2019年 | 37篇 |
2018年 | 45篇 |
2017年 | 33篇 |
2016年 | 67篇 |
2015年 | 121篇 |
2014年 | 124篇 |
2013年 | 165篇 |
2012年 | 156篇 |
2011年 | 197篇 |
2010年 | 119篇 |
2009年 | 105篇 |
2008年 | 138篇 |
2007年 | 198篇 |
2006年 | 177篇 |
2005年 | 159篇 |
2004年 | 132篇 |
2003年 | 131篇 |
2002年 | 156篇 |
2001年 | 27篇 |
2000年 | 18篇 |
1999年 | 29篇 |
1998年 | 37篇 |
1997年 | 27篇 |
1996年 | 24篇 |
1995年 | 26篇 |
1994年 | 21篇 |
1993年 | 32篇 |
1992年 | 19篇 |
1991年 | 20篇 |
1990年 | 18篇 |
1989年 | 17篇 |
1988年 | 23篇 |
1987年 | 22篇 |
1986年 | 22篇 |
1985年 | 17篇 |
1984年 | 15篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 16篇 |
1980年 | 23篇 |
1979年 | 10篇 |
1978年 | 16篇 |
1975年 | 14篇 |
1973年 | 13篇 |
1972年 | 10篇 |
1971年 | 12篇 |
1969年 | 8篇 |
排序方式: 共有2964条查询结果,搜索用时 62 毫秒
971.
Lim JY Li J Sheng H Besser TE Potter K Hovde CJ 《Applied and environmental microbiology》2007,73(4):1380-1382
Long-duration consistently Escherichia coli O157:H7 culture-positive cattle were euthanized and necropsied. Tissue and digesta from along the gastrointestinal tract (GIT) were cultured for the bacteria and examined histologically for lymphoid character. E. coli O157:H7 was detected only at the rectoanal junction mucosa and not at any other GIT location. 相似文献
972.
Munroe W Kingsley C Durazo A Gralla EB Imlay JA Srinivasan C Valentine JS 《Journal of inorganic biochemistry》2007,101(11-12):1875-1882
A variety of manganese-containing coordination compounds, frequently termed superoxide dismutase (SOD) mimics, have been reported to have SOD activity in vitro and to be effective at improving conditions related to increased oxidative stress in multicellular organisms. We tested the effectiveness of several of these compounds in substituting for authentic SOD enzymes in two simple systems--the prokaryote Escherichia coli and the single-celled eukaryote, Saccharomyces cerevisiae--where strains are available that completely lack cytoplasmic SOD activity and are thus significantly impaired in their ability to grow aerobically. Most of the compounds tested, including Euk-8 and Euk-134, manganese salen derivatives developed by Eukarion; M40403, a manganese complex of a bis(cyclohexylpyridine)-substituted macrocyclic ligand developed by Metaphore; and several manganese porphyrin derivatives, were ineffective in both systems. Only the manganese tetrapyridyl porphyrin complex MnTM-2-PyP and two close relatives were effective in rescuing aerobic growth of E. coli lacking SOD, and, in the case of sod1Delta yeast, only MnTM-2-PyP itself was fully effective. Surprisingly, several compounds reported to be beneficial in other in vivo model systems (Euk-8, Euk-134, M40403) were actually toxic to these organisms lacking SOD, although they had no effect on the wild-type parent strains. Our results suggest the possibility that the beneficial effects of some of the so-called "SOD mimic drugs" may be due to some property other than in vivo superoxide dismutase activity. 相似文献
973.
Ramchandra R Barrett CJ Guild SJ McBryde F Malpas SC 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,292(4):R1479-R1485
Nitric oxide levels are diminished in hypertensive patients, suggesting nitric oxide might have an important role to play in the development of hypertension. Chronic blockade of nitric oxide leads to hypertension that is sustained throughout the period of the blockade in baroreceptor-intact animals. It has been suggested that the sympathetic nervous system is involved in the chronic increase in blood pressure; however, the evidence is inconclusive. We measured renal sympathetic nerve activity and blood pressure via telemetry in rabbits over 7 days of nitric oxide blockade. Nitric oxide blockade via N(omega)-nitro-L-arginine methyl ester (L-NAME) in the drinking water (50 mg x kg(-1) x day(-1)) for 7 days caused a significant increase in arterial pressure (7 +/- 1 mmHg above control levels; P < 0.05). While the increase in blood pressure was associated with a decrease in heart rate (from 233 +/- 6 beats/min before the L-NAME to 202 +/- 6 beats/min on day 7), there was no change in renal sympathetic nerve activity (94 +/- 4 %baseline levels on day 2 and 96 +/- 5 %baseline levels on day 7 of L-NAME; baseline nerve activity levels were normalized to the maximum 2 s of nerve activity evoked by nasopharyngeal stimulation). The lack of change in renal sympathetic nerve activity during the L-NAME-induced hypertension indicates that the renal nerves do not mediate the increase in blood pressure in conscious rabbits. 相似文献
974.
Sumanasekera WK Sumanasekera GU Mattingly KA Dougherty SM Keynton RS Klinge CM 《American journal of physiology. Cell physiology》2007,293(2):C566-C573
Postflight orthostatic intolerance (POI) was reported to be higher in female than male astronauts and may result from sex-dependent differences in endothelial cell (EC) barrier permeability. Here the effect of 17-estradiol (E2) and dihydrotestosterone (DHT) on the expression of the tight junction protein occludin, EC barrier function, and MAPK activation over time was tested after subjecting human umbilical vein EC (HUVEC) to brief hypergravity identical to that experienced by astronauts during liftoff (LO) into space. After LO hypergravity, HUVEC showed a time-dependent decrease in occludin correlating with an increase in paracellular permeability and a decrease in transendothelial electrical resistance, indicating a decrease in EC barrier function. LO hypergravity inhibited MAPK activation, which remained suppressed 4 h after LO. Inhibition of MAPK activation correlated with decreased phosphotyrosine occludin, decreased cytochrome-c oxidase activity, and increased paracellular permeability, suggesting a mechanism by which LO hypergravity decreased EC barrier function. Time-dependent differences in MAPK activation, decreased occludin, and EC barrier function between HUVEC treated with E2 vs. DHT were observed. HUVEC showed delayed activation of MAPK with DHT, i.e., 4 h rather than 2 h for E2, which correlated with decreased paracellular permeability and the observed sex differences in POI in astronauts. These data temporally separate E2 and DHT effects in HUVEC and provide evidence for the possible protective roles of sex steroids on EC function after brief exposure to low hypergravity. paracellular permeability; estrogen; androgen 相似文献
975.
Shu Y Rintala-Maki ND Wall VE Wang K Goard CA Langdon CE Sutherland LC 《Cell biochemistry and function》2007,25(6):643-653
RBM5/LUCA-15/H37 is a nuclear SR-related RNA binding protein with the ability to modulate both apoptosis and the cell cycle, and retard tumour formation. How RBM5 functions to carry out these, potentially interrelated, biological activities is unknown. Since reversible phosphorylation has been shown to play an important role in the regulation of SR protein function, apoptosis and cell cycle control, in an attempt to elucidate the underlying mechanisms regulating RBM5 function, the phosphorylation status of RBM5 was investigated. Whole cell lysate from growing cell cultures was treated with the broad phosphatase spectrum of CIP, resulting in a decrease in the molecular mass of RBM5. A similar decrease in molecular mass, of a subset of RBM5 proteins, was observed during growth factor deprivation, in a manner consistent with partial dephosphorylation of RBM5. Molecular mass increased upon growth factor addition, demonstrating that this apoptosis-associated alteration in molecular mass was a reversible process. Immunoprecipitation and mutagenesis experiments strongly suggested that phosphotyrosines are not present in RBM5 under normal growth conditions, and that serine 69 is phosphorylated, but not by Akt kinase. Taken together, these results suggest that reversible phosphorylation of RBM5 is a mechanism capable of regulating RBM5 participation in modulating apoptosis, and perhaps tumour suppression. 相似文献
976.
977.
978.
Tetrahymena POT1a regulates telomere length and prevents activation of a cell cycle checkpoint
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 POT1/TEBP telomere proteins are a group of single-stranded DNA (ssDNA)-binding proteins that have long been assumed to protect the G overhang on the telomeric 3' strand. We have found that the Tetrahymena thermophila genome contains two POT1 gene homologs, POT1a and POT1b. The POT1a gene is essential, but POT1b is not. We have generated a conditional POT1a cell line and shown that POT1a depletion results in a monster cell phenotype and growth arrest. However, G-overhang structure is essentially unchanged, indicating that POT1a is not required for overhang protection. In contrast, POT1a is required for telomere length regulation. After POT1a depletion, most telomeres elongate by 400 to 500 bp, but some increase by up to 10 kb. This elongation occurs in the absence of further cell division. The growth arrest caused by POT1a depletion can be reversed by reexpression of POT1a or addition of caffeine. Thus, POT1a is required to prevent a cell cycle checkpoint that is most likely mediated by ATM or ATR (ATM and ATR are protein kinases of the PI-3 protein kinase-like family). Our findings indicate that the essential function of POT1a is to prevent a catastrophic DNA damage response. This response may be activated when nontelomeric ssDNA-binding proteins bind and protect the G overhang. 相似文献
979.
Terzian T Wang Y Van Pelt CS Box NF Travis EL Lozano G 《Molecular and cellular biology》2007,27(15):5479-5485
The tumor suppressor p53 is inactivated by multiple mechanisms that include mutations of the p53 gene itself and increased levels of the p53 inhibitors MDM2 and MDM4. Mice lacking Mdm2 or Mdm4 exhibit embryo-lethal phenotypes that are completely rescued by concomitant deletion of p53. Here we show that Mdm2 and Mdm4 haploinsufficiency leads to increased p53 activity, exhibited as increased sensitivity to DNA damage and decreased transformation potential. Moreover, in in vivo tumor development, Emu-myc Mdm4+/- mice show a delayed onset of B-cell lymphomas compared to Emu-myc mice. Additionally, Mdm2+/- Mdm4+/- double-heterozygous mice are not viable and exhibit defects in hematopoiesis and cerebellar development. The defects in Mdm2+/- Mdm4+/- mice are corrected by deletion of a single p53 allele. These findings highlight the exquisite sensitivity of p53 to Mdm2 and Mdm4 levels and suggest that some cell types may be more sensitive to therapeutic drugs that inhibit the Mdm-p53 interaction. 相似文献
980.