全文获取类型
收费全文 | 424篇 |
免费 | 17篇 |
出版年
2022年 | 11篇 |
2021年 | 12篇 |
2020年 | 9篇 |
2019年 | 9篇 |
2018年 | 14篇 |
2017年 | 11篇 |
2016年 | 18篇 |
2015年 | 19篇 |
2014年 | 22篇 |
2013年 | 39篇 |
2012年 | 43篇 |
2011年 | 38篇 |
2010年 | 18篇 |
2009年 | 25篇 |
2008年 | 25篇 |
2007年 | 21篇 |
2006年 | 24篇 |
2005年 | 19篇 |
2004年 | 9篇 |
2003年 | 9篇 |
2002年 | 18篇 |
2001年 | 1篇 |
2000年 | 6篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1984年 | 1篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有441条查询结果,搜索用时 31 毫秒
71.
Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: Therapeutic potential of NOX2 and p38MAPK inhibitors
下载免费PDF全文
![点击此处可从《Journal of cellular physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
72.
Increasing autophagy and blocking Nrf2 suppress laminopathy‐induced age‐dependent cardiac dysfunction and shortened lifespan
下载免费PDF全文
![点击此处可从《Aging cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shruti Bhide Adriana S. Trujillo Maureen T. O'Connor Grant H. Young Diane E. Cryderman Sahaana Chandran Mastaneh Nikravesh Lori L. Wallrath Girish C. Melkani 《Aging cell》2018,17(3)
Mutations in the human LMNA gene cause a collection of diseases known as laminopathies. These include myocardial diseases that exhibit age‐dependent penetrance of dysrhythmias and heart failure. The LMNA gene encodes A‐type lamins, intermediate filaments that support nuclear structure and organize the genome. Mechanisms by which mutant lamins cause age‐dependent heart defects are not well understood. To address this issue, we modeled human disease‐causing mutations in the Drosophila melanogaster Lamin C gene and expressed mutant Lamin C exclusively in the heart. This resulted in progressive cardiac dysfunction, loss of adipose tissue homeostasis, and a shortened adult lifespan. Within cardiac cells, mutant Lamin C aggregated in the cytoplasm, the CncC(Nrf2)/Keap1 redox sensing pathway was activated, mitochondria exhibited abnormal morphology, and the autophagy cargo receptor Ref2(P)/p62 was upregulated. Genetic analyses demonstrated that simultaneous over‐expression of the autophagy kinase Atg1 gene and an RNAi against CncC eliminated the cytoplasmic protein aggregates, restored cardiac function, and lengthened lifespan. These data suggest that simultaneously increasing rates of autophagy and blocking the Nrf2/Keap1 pathway are a potential therapeutic strategy for cardiac laminopathies. 相似文献
73.
Adedapo Adedayo Adeniran Mubo Adeola Sonibare Girish Halemirle Rajacharya Shashi Kumar 《Plant Cell, Tissue and Organ Culture》2018,132(2):343-357
Wild tubers of Dioscorea bulbifera (Db) and Dioscorea hirtiflora (Dh) mainly used as sources of famine food and in herbal preparations are often indiscriminately collected in Africa and Asia. Therefore, there is the need to complement wild sourcing of the tubers to promote their conservation. The present study reports in vitro tuberous induction (80%) for the first time from Dh cultured on MS?+?NAA (2.5 mg/L) with IC50 of 472.5?±?1.77 µg/mL using DPPH, whereas tuberous root (60%) from Db on MS?+?Kn (2.5 mg/L)?+?NAA (0.25 mg/L) had IC50 of 26.97?±?1.00 µg/mL. Genetic fidelity assessment of in vitro plants compared to the wild plants revealed similar amplicon size of amplified DNA using trnH–psbA and rbcL. Similarly, micromorphological diagnostic features like oil gland, crystals (raphides), trichome and stomata type were obtained from the epidermal peels of the wild and in vitro plants. The ethyl acetate (EtOAc) extract of the flesh of Dh (wild) had the highest catechin content (108.3?±?0.69 µg/g DW). Protocatechuic acid was highest in the methanol (MeOH) extract of the flesh of Dh (0.42?±?0.02 µg/g DW), while it was detected in trace amount in the in vitro tuberous roots of MeOH extracts of Dh treated with NAA. The in vitro protocol developed in this study could be employed to multiply Dioscorea bulbifera L. and Dioscorea hirtiflora Benth. to offer genetically stable clones for the optimization of bioactive compounds and germplasms conservation. 相似文献
74.
Aparna S Joshi Girish M Sharangpani Kyle Porter Sedigheh Keyhani Carl Morrison Amitabha S Basu Gauri A Gholap Abhi S Gholap Sanford H Barsky 《Cytometry. Part A》2007,71(5):273-285
BACKGROUND: Immunocytochemical methods for quantitating Her-2/neu immunoreactivity rest on subjective semi-quantitative interpretations with resulting interobserver, intraobserver, and fatigue variability. METHODS: To standardize and quantitate measurements of Her-2/neu immunoreactivity, we created epithelial-recognition and specific membrane-recognition algorithms, which could image breast cancer cells against a background of stroma, compartmentalize the cancer cell into nucleus, cytoplasm and membrane, and quantitate the degree of Her-2/neu membrane immunoreactivity based on both gray scale intensity and RGB colorimetric determinations. Image acquisition utilized either scanner or microscope with attached camera with a resolution of 20 pixels/10 microm. Areas of 150 whole slides were screened and the regions of interest manually selected for image processing. Three hundred TMA cores were directly processed. Images were acquired by jpg conversion of svs virtual slides or direct jpg photomicrograph capture. Images were then assessed for quality and processed. RESULTS: The digital algorithms successfully created a semi-automated imaging system whose algorithm-based ordinal values for Her-2/neu both strongly correlated with the subjective measurements (intraclass correlation: 0.84; 95% confidence interval: 0.79-0.89) yet exhibited no run variability. In addition, the algorithms generated immunocytochemical measurements of Her-2/neu on an expanded continuous scale, which more reliably distinguished true Her-2/neu positivity from true Her-2/neu negativity (determined by FISH) than subjective or algorithmic ordinal scale measurements. Furthermore, the continuous scale measurements could better resolve different levels of Her-2/neu overexpression than either subjective or algorithmic ordinal interpretation. Other semi-automated analysis systems have been used to measure Her-2/neu and other cellular immunoreactivities, but these either have required proprietary hardware or have been based on luminosity differences alone. In contrast, our algorithms are independent of proprietary hardware and are based on not just luminosity but also many other imaging properties including epithelial recognition and membrane morphology. CONCLUSION: These features provide a more accurate, versatile, and robust imaging analysis platform. 相似文献
75.
Girish Daswani 《The journal of the Royal Anthropological Institute》2016,22(1):108-126
The anthropological study of value has gained much currency in recent years. This article speaks to the importance of Pentecostal practices in understanding the qualitative aspects of value in Ghana. It demonstrates how practices relating to wealth accumulation and redistribution are in interaction with ethical evaluations about the character of charismatic Christian prophets. The moral evaluation of wealth of certain prophets, and the links perceived between their use of wealth and their character, tell us something about the moral climate in contemporary Ghanaian society, where wealth cannot simply be measured quantitatively (through acquiring riches), but also ought to be assessed qualitatively (discerned through the quality of one's acts). 相似文献
76.
ERK5 is involved in proliferation of vascular smooth muscle cells (VSMC). The proliferative actions of insulin and angiotensin-II (A-II) in VSMC are mediated in part by ERK1/2. We hypothesized that insulin and A-II also regulate ERK5 activity in VSMC. Acute treatment (<60min) with insulin or A-II increased phosphorylation of ERK1/2 at 15min and ERK5 at 5min. Chronic treatment (< or = 8h) with insulin increased ERK1/2 phosphorylation by 4h and ERK5 by 8h. A-II-stimulated phosphorylation of ERK1/2 by 8h and ERK5 by 4h. The EC(50) for insulin treatment effecting ERK1/2 and ERK5 phosphorylation was 1.5 and 0.1nM, whereas the EC(50) for A-II was 2nM, each. Insulin plus A-II induced an additive effect only on ERK5 phosphorylation. Inhibition of insulin- and A-II-stimulated phosphorylation of ERK5 and ERK1/2 by PD98059 and Wortmannin exhibited differential and time-dependent effects. Taken together, these data indicate that insulin and A-II regulate the activity of ERK5, but different from that seen for ERK1/2. 相似文献
77.
Nagarajan Muthukaman Macchindra Tambe Mahamadhanif Shaikh Dnyandeo Pisal Sanjay Deshmukh Shital Tondlekar Neelam Sarode Lakshminarayana Narayana Jitendra M. Gajera Vidya G. Kattige Srinivasa Honnegowda Vikas Karande Abhay Kulkarni Dayanidhi Behera Satyawan B. Jadhav Girish S. Gudi Neelima Khairatkar-Joshi Laxmikant A. Gharat 《Bioorganic & medicinal chemistry letters》2017,27(11):2594-2601
A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE2 release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F = 33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model. 相似文献
78.
Therapeutic antibodies include polyclonal immunoglobulins isolated from regular or high-titered human plasma, sera from immunized animals, and monoclonal antibodies. This array of therapeutic antibodies is used for the prevention and treatment of many infectious diseases, antibody immunodeficiencies, autoimmune and inflammatory diseases, neurological disorders, and cancers. Polyclonal human immunoglobulins are available for intramuscular injection (IGIM), intravenous infusion (IGIV) and subcutaneous infusion (SCIG). We review these products and detail the therapeutic use of polyclonal human antibodies in the treatment of antibody immunodeficiencies, including their occasional local side effects (tenderness, sterile abscesses), minor systemic side effects (chills, muscle aches, malaise, headaches) and major side effects (aseptic meningitis, nephropathy, thrombosis). 相似文献
79.
Hameeda Sultana Girish Neelakanta Francisco Rivero Angelika A. Noegel 《Experimental cell research》2009,315(2):127-1518
Large-scale gene expression analysis has been applied recently to uncover groups of genes that are co-regulated in particular processes. Here we undertake such an analysis on CAP, a protein that participates in the regulation of the actin cytoskeleton and in cAMP signaling in Dictyostelium. microarray analysis revealed that loss of CAP altered the expression of many cytoskeletal components. One of these, the Rho GDP-dissociation inhibitor RhoGDI1, was analyzed further. RhoGDI1 null cells expressed lower amounts of CAP, which failed to accumulate predominantly at the cell cortex. To further position CAP in the corresponding signal transduction pathways we studied CAP localization and cellular functioning in mutants that have defects in several signaling components. CAP showed correct localization and dynamics in all analyzed strains except in mutants with deficient cAMP dependent protein kinase A activity, where CAP preferentially accumulated in crown shaped structures. Ectopic expression of CAP improved the efficiency of phagocytosis in Gβ-deficient cells and restored the pinocytosis, morphology and actin distribution defects in a PI3 kinase double mutant (pi3k1/2 null). Our results show that CAP acts at multiple crossroads and links signaling pathways to the actin cytoskeleton either by physical interaction with cytoskeletal components or through regulation of their gene expression. 相似文献
80.
Rinki Ratnapriya Parthasarthy Satishchandra S. Dilip Girish Gadre Anuranjan Anand 《Human genetics》2009,126(5):677-683
Hot water epilepsy is a reflex or sensory epilepsy in which seizures are triggered by the stimulus of bathing in hot water.
Although there is evidence of a genetic basis to its etiology, no gene associated with this disorder has so far been found.
In order to identify the genetic locus involved in the pathophysiology of hot water epilepsy, we performed a genome-wide linkage
analysis in a four-generation family manifesting the disorder in an autosomal dominant manner. Significant linkage was detected
on chromosome 4q24-q28, with the highest two-point LOD score of 3.50 at recombination value (θ) of 0 for the marker D4S402. Centromere-proximal and centromere-distal boundaries of this locus were defined by the markers
D4S1572 and D4S2277, respectively. The critical genetic interval spans 22.5 cM and corresponds to about 24 megabases of DNA.
The genes NEUROG2, ANK2, UGT8 and CAMK2D, which are known to be expressed in human brain, are strong positional candidates and we propose to examine these and other
genes in the locus to identify the causative gene for this intriguing form of epilepsy. 相似文献