全文获取类型
收费全文 | 586篇 |
免费 | 35篇 |
出版年
2023年 | 5篇 |
2022年 | 5篇 |
2021年 | 20篇 |
2020年 | 14篇 |
2019年 | 15篇 |
2018年 | 19篇 |
2017年 | 11篇 |
2016年 | 19篇 |
2015年 | 31篇 |
2014年 | 37篇 |
2013年 | 38篇 |
2012年 | 55篇 |
2011年 | 42篇 |
2010年 | 28篇 |
2009年 | 18篇 |
2008年 | 26篇 |
2007年 | 40篇 |
2006年 | 29篇 |
2005年 | 32篇 |
2004年 | 30篇 |
2003年 | 19篇 |
2002年 | 17篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有621条查询结果,搜索用时 765 毫秒
561.
562.
Inostroza-Blancheteau C Rengel Z Alberdi M de la Luz Mora M Aquea F Arce-Johnson P Reyes-Díaz M 《Molecular biology reports》2012,39(3):2069-2079
Aluminum (Al) toxicity is a primary limitation to plant growth on acid soils. Root meristems are the first site for toxic
Al accumulation, and therefore inhibition of root elongation is the most evident physiological manifestation of Al toxicity.
Plants may resist Al toxicity by avoidance (Al exclusion) and/or tolerance mechanisms (detoxification of Al inside the cells).
The Al exclusion involves the exudation of organic acid anions from the root apices, whereas tolerance mechanisms comprise
internal Al detoxification by organic acid anions and enhanced scavenging of free oxygen radicals. One of the most important
advances in understanding the molecular events associated with the Al exclusion mechanism was the identification of the ALMT1 gene (Al-activated malate transporter) in Triticum aestivum root cells, which codes for a plasma membrane anion channel that allows efflux of organic acid anions, such as malate, citrate
or oxalate. On the other hand, the scavenging of free radicals is dependent on the expression of genes involved in antioxidant
defenses, such as peroxidases (e.g. in Arabidopsis
thaliana and Nicotiana tabacum), catalases (e.g. in Capsicum annuum), and the gene WMnSOD1 from T. aestivum. However, other recent findings show that reactive oxygen species (ROS) induced stress may be due to acidic (low pH) conditions
rather than to Al stress. In this review, we summarize recent findings regarding molecular and physiological mechanisms of
Al toxicity and resistance in higher plants. Advances have been made in understanding some of the underlying strategies that
plants use to cope with Al toxicity. Furthermore, we discuss the physiological and molecular responses to Al toxicity, including
genes involved in Al resistance that have been identified and characterized in several plant species. The better understanding
of these strategies and mechanisms is essential for improving plant performance in acidic, Al-toxic soils. 相似文献
563.
Kinases, phosphatases and proteases during sperm capacitation 总被引:1,自引:0,他引:1
Fertilization is the process by which male and female haploid gametes (sperm and egg) unite to produce a genetically distinct individual. In mammals, fertilization involves a number of sequential steps, including sperm migration through the female genital tract, sperm penetration through the cumulus mass, sperm adhesion and binding to the zona pellucida, acrosome exocytosis, sperm penetration through the zona and fusion of the sperm and egg plasma membranes. However, freshly ejaculated sperm are not capable of fertilizing an oocyte. They must first undergo a series of biochemical and physiological changes, collectively known as capacitation, before acquiring fertilizing capabilities. Several molecules are required for successful capacitation and in vitro fertilization; these include bicarbonate, serum albumin (normally bovine serum albumin, BSA) and Ca(2+). Bicarbonate activates the sperm protein soluble adenylyl cyclase (SACY), which results in increased levels of cAMP and cAMP-dependent protein kinase (PKA) activation. The response to bicarbonate is fast and cAMP levels increase within 60?s followed by an increase in PKA activity. Several studies with an anti-phospho-PKA substrate antibody have demonstrated a rapid increase in protein phosphorylation in human, mouse and boar sperm. The target proteins of PKA are not known and the precise role of BSA during capacitation is unclear. Most of the studies provide support for the idea that BSA acts by removing cholesterol from the sperm. The loss of cholesterol has been suggested to affect the bilayer of the sperm plasma membrane making it more fusogenic. The relationship between cholesterol loss and the activation of the cAMP/PKA pathway is also unclear. During early stages of capacitation, Ca(2+) might be involved in the stimulation of SACY, although definitive proof is lacking. Protein tyrosine phosphorylation is another landmark of capacitation but occurs during the late stages of capacitation on a different time-scale from cAMP/PKA activation. Additionally, the tyrosine kinases present in sperm are not well characterized. Although protein phosphorylation depends upon the balanced action of protein kinases and protein phosphatase, we have even less information regarding the role of protein phosphatases during sperm capacitation. Over the last few years, several reports have pointed out that the ubiquitin-proteasome system might play a role during sperm capacitation, acrosome reaction and/or sperm-egg fusion. In the present review, we summarize the information regarding the role of protein kinases, phosphatases and the proteasome during sperm capacitation. Where appropriate, we give examples of the way that these molecules interact and regulate each other's activities. 相似文献
564.
565.
Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin 总被引:2,自引:0,他引:2
Winbanks CE Weeks KL Thomson RE Sepulveda PV Beyer C Qian H Chen JL Allen JM Lancaster GI Febbraio MA Harrison CA McMullen JR Chamberlain JS Gregorevic P 《The Journal of cell biology》2012,197(7):997-1008
Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2. Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling. Expression of constitutively active Smad3 not only markedly prevented skeletal muscle growth induced by follistatin but also potently suppressed follistatin-induced Akt/mTOR/S6K signaling. Importantly, the regulation of Smad3- and mTOR-dependent events by follistatin occurred independently of overexpression or knockout of myostatin, a key repressor of muscle development that can regulate Smad3 and mTOR signaling and that is itself inhibited by follistatin. These findings identify a critical role of Smad3/Akt/mTOR/S6K/S6RP signaling in follistatin-mediated muscle growth that operates independently of myostatin-driven mechanisms. 相似文献
566.
Juan Patricio Anchordoquy Raúl Martín Lizarraga Juan Mateo Anchordoquy Noelia Nikoloff Diana Esther Rosa Mariana Carolina Fabra Pilar Peral-García Cecilia Cristina Furnus 《Reproductive biology》2019,19(4):349-355
Glutathione (GSH) is an antioxidant synthesized from three constitutive amino acids (CAA): cysteine (Cys), glycine (Gly) and glutamate (Glu). Glutathione plays an important role in oocyte maturation, fertilization and early embryo development. This study aimed to investigate the effect of Cys (0.6 mM), Gly (0.6 mM) and Glu (0.9 mM) supplementation during in vitro fertilization (IVF) of cattle oocytes. In a Pilot Experiment, de novo synthesis of GSH in bovine zygote was evaluated using a modified TALP medium prepared without MEM-essential and MEM-non-essential amino acids (mTALP): mTALP + CAA (constitutive amino acids); mTALP + CAA+5 mMBSO (buthionine sulfoximide); mTALP + Cys + Gly; mTALP + Cys + Glu and mTALP + Gly + Glu. This evidence led us to investigate the impact of CAA supplementation to TALP medium (with essential and non-essential amino acids) on zygote viability, lipid peroxidation, total intracellular GSH content (include reduced and oxidized form; GSH-GSSG), pronuclear formation in zygotes and subsequent embryo development. IVF media contained a) TALP; b) TALP + Cys + Gly + Glu (TALP + CAA); c) TALP + Cys + Gly; d) TALP + Cys + Glu; e) TALP + Gly + Glu, were used. Total GSH-GSSG concentration was increased in TALP, TALP + CAA, and TALP + Cys + Gly. The viability of zygote was similar among treatments. Lipid peroxidation was increased in zygote fertilized with TALP + Cys + Gly; TALP + Cys + Glu; TALP + Gly + Glu and TALP + CAA. The percentage of penetrated oocytes decreased in TALP + CAA and TALP + Cys + Gly. The cleavage rate was lower in TALP + CAA and TALP + Gly + Glu. The percentage of embryos developing to the blastocyst stage was lower in TALP + Cys + Glu and TALP + CAA. In conclusion, we have demonstrated the synthesis of GSH during IVF. However, Cys, Gly and Glu supplementation to TALP medium had negative effects on embryonic development. 相似文献
567.
Melatonin (N-acetyl-5-methoxytryptamine) and its immediate precursor N-acetyl serotonin in the metabolism of tryptophan are free radical scavengers that have been found to protect against non-enzymatic lipid peroxidation in many experimental models. By contrast, little is known about the antioxidant ability of these indoleamines against NADPH enzymatic lipid peroxidation. The light emission produced by rat-liver microsomes, expressed as total cpm during 180 min of incubation at 37 degrees C, was two-fold greater in the presence of ascorbate (0.4mM) when compared with NADPH (0.2 mM). Maximal peaks of light emission produced by microsomes lipid peroxidized with ascorbic-Fe(2+) or NADPH and expressed as cpm were 354,208 (at 60 min) and 135,800 (at 15 min), respectively. During non-enzymatic lipid peroxidation a decrease of total chemiluminescence (inhibition of lipid peroxidation) was observed when increasing concentrations of melatonin were added to liver microsomes. The protective effect was concentration-dependent. The inhibition observed in light emission was coincident with the protection of the most PUFAs. Preincubation of microsomes with N-acetyl serotonin reduced these changes very dramatically. Thus, in the presence of both antioxidants (0.36, 0.75, 1.5 mM), light emission percent inhibition during non-enzymatic (ascorbate-Fe(2+)) lipid peroxidation of rat liver microsomes was for melatonin: 6.12, 16.20, 34.88 and for N-acetyl serotonin: 85.10, 88.48, 84.4 respectively. The incubation of rat liver microsomes in the presence of NADPH (0.36, 0.75, 1.5 mM) produce a sudden increase of chemiluminescence that gradually increased and reached a maximal value at about 15 min; however, N-acetyl serotonin reduced these changes very efficiently. 相似文献
568.
Objective To determine the effects of iron-deficiency anemia on the development of non-rapid-eye-movement (NREM) sleep stages, as indexed
by sleep spindles.
Study design Patterns of sleep spindles during NREM sleep stages 2 and 3–4 (slow-wave-sleep, SWS) were compared in 26 otherwise healthy
6-month-old Chilean infants with iron-deficiency anemia and 18 non-anemic control infants. From polygraphic recordings, EEG
activity was analyzed for sleep spindles to assess their number (density), duration, frequency, and inter-spindle interval.
Results Iron-deficient anemic infants differed from the control group by having sleep spindles with reduced density, lower frequency,
and longer inter-spindle intervals in NREM sleep stage 2 and SWS.
Conclusions These results provide evidence of delayed sleep spindle patterns in iron-deficient anemic infants, suggesting that iron is
an essential micronutrient for the normal progression of NREM sleep pattern development in the human.
Special issue dedicated to Dr. Moussa Youdim. 相似文献
569.
570.
Isabel Elematore Patricio Gonzalez-Hormazabal Jose M. Reyes Rafael Blanco Teresa Bravo Octavio Peralta Fernando Gomez Enrique Waugh Sonia Margarit Gladys Ibañez Carmen Romero Janara Pakomio Gigia Roizen Gabriella A. Di Capua Lilian Jara 《Molecular biology reports》2014,41(6):3715-3722
Recent Genome-Wide Association Studies have identified several single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) among women of Asian, European, and African-American ancestry. Nevertheless, the contribution of these variants in the South American population is unknown. Furthermore, there is little information about the effect of these risk alleles in women with early BC diagnosis. In the present study, we evaluated the association between rs3803662 (TOX3, also known as TNRC9), rs13387042 (2q35), and rs13281615 (8q24) with BC risk in 344 Chilean BRCA1/2-negative BC cases and in 801 controls. Two SNPs, rs3803662 and rs13387042, were significantly associated with increased BC risk in familial BC and in non-familial early-onset BC. The risk of BC increased in a dose-dependent manner with the number of risk alleles (P-trend < 0.0001 and 0.0091, respectively). The odds ratios for BC in familial BC and in early-onset non-familial BC were 3.76 (95 %CI 1.02–13.84, P = 0.046) and 8.0 (95 %CI 2.20–29.04, P = 0.002), respectively, for the maximum versus minimum number of risk alleles. These results indicate an additive effect of the TOX3 rs3803662 and 2q35 rs13387042 alleles for BC risk. We also evaluated the interaction between rs3803662 and rs13387042 SNPs. We observed an additive interaction only in non-familial early-onset BC cases (AP = 0.72 (0.28–1.16), P = 0.001). No significant association was observed for rs13281615 (8q24) with BC risk in women from the Chilean population. The strongly increased risk associated with the combination of low-penetrance risk alleles supports the polygenic inheritance model of BC. 相似文献