全文获取类型
收费全文 | 701篇 |
免费 | 55篇 |
专业分类
756篇 |
出版年
2024年 | 2篇 |
2023年 | 6篇 |
2022年 | 18篇 |
2021年 | 31篇 |
2020年 | 15篇 |
2019年 | 23篇 |
2018年 | 23篇 |
2017年 | 14篇 |
2016年 | 27篇 |
2015年 | 40篇 |
2014年 | 45篇 |
2013年 | 59篇 |
2012年 | 54篇 |
2011年 | 60篇 |
2010年 | 30篇 |
2009年 | 27篇 |
2008年 | 31篇 |
2007年 | 38篇 |
2006年 | 36篇 |
2005年 | 23篇 |
2004年 | 22篇 |
2003年 | 18篇 |
2002年 | 18篇 |
2001年 | 13篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1989年 | 4篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1982年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1967年 | 1篇 |
1963年 | 1篇 |
1960年 | 2篇 |
1957年 | 1篇 |
1948年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有756条查询结果,搜索用时 13 毫秒
101.
Protein kinase C inhibits insulin-induced Akt activation in vascular smooth muscle cells. 总被引:2,自引:0,他引:2
E D Motley S M Kabir K Eguchi A L Hicks C D Gardner C M Reynolds G D Frank S Eguchi 《Cellular and molecular biology, including cyto-enzymology》2001,47(6):1059-1062
Protein kinase C (PKC) activation, enhanced by hyperglycemia, is associated with many tissue abnormalities observed in diabetes. Akt is a serine/threonine kinase that mediates various biological responses induced by insulin. We hypothesized that the negative regulation of Akt in the vasculature by PKC could contribute to insulin resistant states and, may therefore play a role in the pathogenesis of cardiovascular disease. In this study, we specifically looked at the ability of PKC to inhibit Akt activation induced by insulin in cultured rat aortic vascular smooth muscle cells (VSMCs). Activation of Akt was determined by immunoblotting with a phospho-Akt antibody that selectively recognizes Ser473 phosphorylated Akt. A PKC activator, phorbol 12-myristate 13-acetate (PMA), inhibited insulin-dependent Akt phosphorylation. However, PMA did not inhibit platelet-derived growth factor (PDGF)-induced activation of Akt. We further showed that the PKC inhibitor, G06983, blocked the PMA-induced inhibition of Akt phosphorylation by insulin. In addition, we demonstrated that PMA inhibited the insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). From these data, we conclude that PKC is a potent negative regulator of the insulin signal in the vasculature, which indicate an important role of PKC in the development of insulin resistance in cardiovascular disease. 相似文献
102.
Lee Ann MacMillan-Crow Danielle L. Cruthirds Kabir M. Ahki Paul W. Sanders John A. Thompson 《Free radical biology & medicine》2001,31(12):1603-1608
Endogenous tyrosine nitration and inactivation of manganese superoxide dismutase (MnSOD) has previously been reported to occur during end-stage human renal allograft rejection. In order to determine whether nitration and inactivation of this critical mitochondrial protein might play a contributory role in the onset of transplant rejection, we employed a rodent model of Chronic Allograft Nephropathy (or CAN). Using this model we followed kidney function from 2–52 weeks post-transplant and correlated graft function with levels of nitration in the renal allograft. Tyrosine nitration of both glomerular and tubular structures occurred at 2 weeks post-transplant. At later times (16 weeks) post-transplant, tyrosine nitration appeared to be confined to tubular structures; however glomerular nitration returned at 52 weeks post-transplant. Interestingly, nitration and inactivation of MnSOD occurs prior to the onset of renal dysfunction in this rat model of chronic allograft nephropathy (2 weeks versus 16 weeks post-transplant). Furthermore, we have identified an additional mitochondrial protein, cytochrome c, as being endogenously nitrated during chronic rejection. The kinetics of cytochrome c nitration lagged behind MnSOD nitration and inactivation (4 weeks compared to 2 weeks); suggesting that loss of MnSOD activity likely contributes to elevation of the nitrating species and further nitration of other targets. 相似文献
103.
M. A. Bari S. A. Prity U. Das M. S. Akther S. A. Sajib M. A. Reza A. H. Kabir 《Plant biology (Stuttgart, Germany)》2020,22(3):472-479
- Cadmium (Cd) is detrimental to crops and the environment. This work examines the natural mechanisms underlying silicon‐ (Si‐)directed Cd detoxification in rice plants.
- The addition of Si to plants under Cd stress caused significant improvements in morphological parameters, chlorophyll score, Fv/Fm and total soluble protein concentration compared to controls, confirming that Si is able to ameliorate Cd‐induced damage in rice plants. This morpho‐physiological evidence was correlated with decreased cell death and electrolyte leakage after Si application.
- The results showed no critical changes in root Cd concentration, while shoot Cd decreased significantly after Si supplementation in comparison with Cd‐stressed rice. Additionally, expression of Cd transporters (OsNRAMP5 and OsHMA2) was significantly down‐regulated while the concentration of phytochelatin, cysteine and glutathione, together with expression of OsPCS1 (phytochelatin synthase) in roots of Cd‐stressed rice was significantly induced when subjected to Si treatment. This confirms that the alleviation of Cd stress is not only limited to the down‐regulation of Cd transporters but also closely related to the phytochelatin‐driven vacuolar storage of Cd in rice roots.
- The enzymatic analysis further revealed the role of SOD and GR enzymes in protecting rice plants from Cd‐induced oxidative harm. These findings suggest a mechanistic basis in rice plants for Si‐mediated mitigation of Cd stress.
104.
A.U. Mahmud A.K.M.A. Hoque Md. Rejwan Bhuiyan M.E. Kabir Asif Mahmud 《Archives Of Phytopathology And Plant Protection》2013,46(19):2295-2304
A field experiment was conducted to investigate the effect of some management practices to minimise jute yellow mosaic virus disease. The management practices were employed at natural condition and placed randomly with four replications. The treatments were spraying malathion 57 EC, rouging and field sanitation, top dressing of nitrogenous fertiliser, mulching with straw and untreated control. The highest percentage of mosaic incidence was recorded in control and the lowest incidence was recorded in top dressing of nitrogenous fertiliser. Among the treatments, top dressing of nitrogenous fertiliser showed the best performance in terms of increasing yield (3.05?t/ha). The second highest was obtained in rouging and field sanitation which was statistically similar to spraying malathion 57 EC. The best gross margin ($379.02/ha) and increase of gross margin (63.00%) compared to control were achieved in top dressing of nitrogenous fertiliser with the highest benefit-cost ratio (4.84). However, the treatments were found significantly profitable compared to the control indicating the usefulness of the cultural practices in integrated disease management programme for healthy and profitable jute cultivation. 相似文献
105.
Mortality incidence estimation using federal death certificate and natality data with an application to Tay–Sachs disease
下载免费PDF全文
![点击此处可从《Biometrical journal. Biometrische Zeitschrift》网站下载免费的PDF全文](/ch/ext_images/free.gif)
For confidentiality reasons, US federal death certificate data are incomplete with regards to the dates of birth and death for the decedents, making calculation of total lifetime of a decedent impossible and thus estimation of mortality incidence difficult. This paper proposes the use of natality data and an imputation‐based method to estimate age‐specific mortality incidence rates in the face of this missing information. By utilizing previously determined probabilities of birth, a birth date and death date are imputed for every decedent in the dataset. Thus, the birth cohort of each individual is imputed, and the total on‐study time can be calculated. This idea is implemented in two approaches for estimation of mortality incidence rates. The first is an extension of a person‐time approach, while the second is an extension of a life table approach. Monte Carlo simulations showed that both approaches perform well in comparison to the ideal complete data methods, but that the person‐time method is preferred. An application to Tay–Sachs disease is demonstrated. It is concluded that the imputation methods proposed provide valid estimates of the incidence of death from death certificate data without the need for additional assumptions under which usual mortality rates provide valid estimates. 相似文献
106.
Mehran Kausar Saima Siddiqi Muhammad Yaqoob Sajid Mansoor Outi Makitie Asif Mir Chiea Chuen Khor Jia Nee Foo Mariam Anees 《Journal of biomedical science》2018,25(1):82
Introduction
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disease with skeletal fragility and variable extra-skeletal manifestations. To date several point mutations in 18 different genes causing different types of OI have been identified. Mutations in WNT1 compromise activity of the osteoblasts leading to disturbed bone mass accrual, fragility fractures and progressive skeletal abnormalities. The present study was conducted to determine the underlying genetic cause of an autosomal recessive skeletal dysplasia in a large consanguineous family from Chinute, Pakistan.Materials and methods
Blood was collected from 24 individuals of affected family along with clinical data. Homozygosity mapping was performed to confirm consanguinity. SNPs were identified, followed by whole exome and Sanger sequencing. In silico characterization of WNT1 mutation was performed using multiple platforms.Results
Nine affected family members exhibited severe bone deformities, recurrent fractures, short stature and low bone mineral density. SNP array data revealed homozygous segments >?1 Mb in length accounting for 2.1–12.7% of the genome in affected individuals and their siblings and a single 6,344,821 bp homozygous region in all affected individuals on chromosome 12q12-q13. This region includes two potential OI candidate genes WNT1 and VDR. We did whole-exome sequencing for both genes in two patients and identified a novel damaging missense mutation in exon 4 of WNT1: c.1168G?>?T (NM_005430) resulting in p.G324C. Sanger sequencing confirmed segregation of mutation with the disease in family.Conclusion
We report a novel mutation responsible for OI and our investigation expands the spectrum of disease-causing WNT1 mutations and the resulting OI phenotypes.107.
Zinc deficiency tolerance in maize is associated with the up‐regulation of Zn transporter genes and antioxidant activities
下载免费PDF全文
![点击此处可从《Plant biology (Stuttgart, Germany)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M. A. Khatun M. M. Hossain M. A. Bari K. M. Abdullahil M. S. Parvez M. F. Alam A. H. Kabir 《Plant biology (Stuttgart, Germany)》2018,20(4):765-770
- Zinc (Zn) is an essential micronutrient for the growth and development of plants. However, Zn deficiency is a common abiotic stress causing yield loss in crop plants. This study elucidates the mechanisms of Zn deficiency tolerance in maize through physiological and molecular techniques.
- Maize lines tolerant (PAC) and sensitive (DAC) to Zn deficiency were examined physiologically and by atomic absorption spectrometry (AAS). Proteins, H2O2, SOD, POD, membrane permeability and gene expression (using real‐time PCR) of roots and shoots of both maize lines were assessed.
- Zn deficiency had no significant effect on root parameters compared with control plants in PAC and DAC but showed a substantial reduction in shoot parameters in DAC. AAS showed a significant decrease in Zn concentrations in both roots and shoots of DAC but not PAC under Zn deficiency, implying that Zn deficiency tolerance mechanisms exist in PAC. Consistently, total protein and membrane permeability were significantly reduced in DAC but not PAC in both roots and shoots under Zn deficiency in comparison with Zn‐sufficient plants. Real‐time PCR showed that expression of ZmZIP1, ZmZIP4 and ZmIRT1 transporter genes significantly increased in roots of PAC, but not in DAC due to Zn deficiency compared with controls. The H2O2 concentration dramatically increased in roots of DAC but not PAC. Moreover, tolerant PAC showed a significant increase in POD and SOD activity due to Zn deficiency, suggesting that POD‐ and SOD‐mediated antioxidant defence might provide tolerance, at least in part, under Zn deficiency in PAC.
- This study provides an essential background for improving Zn biofortification of maize.
108.
CDK9‐mediated phosphorylation controls the interaction of TIP60 with the transcriptional machinery
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
109.
George Burjanadze Mariam Shengelia Natalia Dachanidze Mariam Mikadze Ketevan Menabde Nana Koshoridze 《Biological Rhythm Research》2018,49(1):61-75
Disturbances in natural Circadian rhythm are well-known stress factors, affecting a range of metabolic pathways in the living body including the brain. Hence, discovery of natural compounds that could help to prevent and cure of adverse changes is very important. One of the recently discussed substances is creatine, that is believed to have anti-stressor properties. Recent paper describes the impact of intraperitoneally injected creatine (140 mg/kg) into rats with a disturbed natural circadian rhythm for an extended period of time (30 days). Markedly, creatine-treated animals show positive changes in open-field behavioral parameters, and an increase in certain antioxidant enzymes’ (SOD, catalase) activity in the hippocampus, whereas the concentration of nitric oxide, H2O2, and Ca2+ are approximated to the control value. Similar findings were also observed in case of Na+/K+- and Ca2+-ATPases. To sum up, the recent findings allow the conclusion that oxidative stress induced by long-term disturbances in natural circadian rhythm is accompanied and likely provoked by an increase in Ca2+-cytotoxicity, which is supposedly normalized by the creatine’s indirect action on the NMDA receptor. Therefore, impact on energy mediating pathways has a positive effect on stabilization of antioxidant and various metabolic systems and protecting hippocampal cells from stress. 相似文献
110.
Md. Zahirul Kabir Hamidah Ghani Saharuddin B. Mohamad Zazali Alias 《Journal of biomolecular structure & dynamics》2018,36(10):2495-2507
Multiple spectroscopic techniques, such as fluorescence, absorption, and circular dichroism along with in silico studies were used to characterize the binding of a potent inhibitor molecule, CCG1423 to the major transport protein, human serum albumin (HSA). Fluorescence and absorption spectroscopic results confirmed CCG1423–HSA complex formation. A strong binding affinity stabilized the CCG1423–HSA complex, as evident from the values of the binding constant (Ka = 1.35 × 106–5.43 × 105 M?1). The KSV values for CCG1423–HSA system were inversely correlated with temperature, suggesting the involvement of static quenching mechanism. Thermodynamic data anticipated that CCG1423–HSA complexation was mainly driven by hydrophobic and van der Waals forces as well as hydrogen bonds. In silico analysis also supported these results. Three-dimensional fluorescence and circular dichroism spectral analysis suggested microenvironmental perturbations around protein fluorophores and structural (secondary and tertiary) changes in the protein upon CCG1423 binding. CCG1423 binding to HSA also showed some protection against thermal denaturation. Site-specific marker-induced displacement results revealed CCG1423 binding to Sudlow’s site I of HSA, which was also confirmed by the computational results. A few common ions were also found to interfere with the CCG1423–HSA interaction. 相似文献