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排序方式: 共有267条查询结果,搜索用时 171 毫秒
121.
A. Karmakar S. Maitra D. Verma B. Chakraborti R. Goswami P. Ghosh S. Sinha K. P. Mohanakumar R. Usha K. Mukhopadhyay 《Neurochemical research》2014,39(5):843-852
Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed behavioral disorder in children with a high frequency of co-morbid conditions like conduct disorder (CD) and oppositional defiant disorder (ODD). These traits are controlled by neurotransmitters like dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of amines, has been reported to be associated with aggression, impulsivity, depression, and mood changes. We hypothesized that MAOA can have a potential role in ADHD associated CD/ODD and analyzed 24 markers in a group of Indo-Caucasoid subjects. ADHD probands and controls (N = 150 each) matched for ethnicity and gender were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Appropriate scales were used for measuring CD and ODD traits. Markers were genotyped by PCR-based methods and data obtained analyzed using the Cocaphase program under UNPHASED. Only eight markers were found to be polymorphic. rs6323 “G” allele showed higher frequencies in ADHD (P = 0.0023), ADHD + CD (P = 0.03) and ADHD + ODD (P = 0.01) as compared to controls. Haplotype analysis revealed statistically significant difference for three haplotypes in ADHD cases (P < 0.02). Statistically significant differences were also noticed for haplotypes in ADHD + CD and ADHD + ODD cases (P < 0.01). LD analysis showed significant variation in different groups. Multidimensionality reduction analysis showed independent as well as interactive effects of markers. Genotypes showed correlation with behavioral problems in ADHD and ADHD + CD. We interpret that MAOA gene variants may contribute to the etiology of ADHD as well as associated co-morbid CD and ODD in this ethnic group. 相似文献
122.
Showkat Ahmad Ganie Joydip Karmakar Rajib Roychowdhury Tapan Kumar Mondal Narottam Dey 《Plant Systematics and Evolution》2014,300(7):1741-1747
A heterogeneous collection of rice genotypes which included seven salt-tolerant rice lines, one salt-sensitive improved line, one wild rice (Oryza rufipogon) and one salt-tolerant wild rice relative (Porteresia coarctata) was screened with ten salt-tolerance-linked simple sequence repeat markers, of which nine were from the Saltol QTL mapped on rice 1st chromosome and the rest one from 8th chromosome, having high phenotypic variance for salt tolerance. Variation in molecular weight (in the form of base pairs) of the different amplified products using RM primers was used to find out the genetic relationship among the studied rice genotypes. Genomic DNA of the studied genotypes was also amplified with a reported allele mining primer for a salt-inducible gene (salT). The amplified products were sequenced and aligned to find out the closeness among the rice lines for the studied gene. Dendrogram derived from marker profiles showed partial similarity with salT gene-derived tree. Commonly, all the salt-tolerant lines were grouped into a single cluster, including IR36 (a salt-sensitive line) to which O. rufipogon (the wild rice) and P. coarctata (the wild rice relative) joined separately. The taxonomic identity and evolutionary relationship among the three groups (rice, wild rice and wild rice relative) were bioinformatically analysed using the nucleotide sequence of the studied salT gene. 相似文献
123.
Surajit Karmakar Subhasree Roy Choudhury Naren L. Banik 《Biochemical and biophysical research communications》2009,388(4):705-1117
Neuroblastoma is the most common extracranial solid tumor in infants and young children. Current treatments are not always effective and new therapies are needed. We examined efficacy of combination of the small molecule Bcl-2 inhibitor HA14-1 (HA) and the dietary isoflavonoid apigenin (APG) in human malignant neuroblastoma cells. Dose-response studies indicated that treatment with HA and APG for 24 h synergistically reduced cell viability in human malignant neuroblastoma SK-N-DZ, SH-SY5Y, and IMR32 cells. For further studies, we selected SK-N-DZ cells that showed the highest sensitivity following treatment with 2.5 μM HA, 100 μM APG, or combination (2.5 μM HA + 100 μM APG). Wright staining showed increase in morphological features of apoptosis. Cell cycle distribution and Annexin V assay showed that combination therapy caused more apoptosis than either treatment alone. Western blotting revealed that combination therapy downregulated angiogenic factors and also induced extrinsic pathway of apoptosis with activation of caspase-8 for Bid cleavage to tBid. Alterations in Bax and Bcl-2 levels resulted in an increase in Bax:Bcl-2 ratio to activate intrinsic pathway of apoptosis with mitochondrial release of cytochrome c into the cytosol and activation of proteases. Increases in calpain and caspase-3 activities generated 145 kD spectrin break down product (SBDP) and 120 kD SBDP, respectively. Results showed that combination of HA and APG could be used for downregulation of angiogenic factors and activation of extrinsic and intrinsic pathways of apoptosis in malignant neuroblastoma cells. 相似文献
124.
125.
In this study of the genetics of dermatoglyphic asymmetry, we collected bilateral finger and palm prints of 824 individuals from 200 families including 2 generations from an endogamous caste (Vaidya) in Barasat, North 24-Parganas District, West Bengal. Two main types of asymmetry (fluctuating asymmetry and directional asymmetry) were calculated between the two hands. The study includes familial correlation between first-degree relatives, principal-components analysis, and maximum-likelihood-based heritabilities (by pedigree analysis). We found, first, that familial correlations in all possible pairs of relationships (except spouse correlation) were weak but positive; some were even statistically significant. No indication of assortative mating was observed, but the influence of maternal environment could not be discarded. The results also showed that X-chromosome linkage does not seem to be involved. A second major finding is that five principal factors could be extracted from all these asymmetric traits, explaining 74.207% of the overall cumulative variance. Asymmetry of finger and palmar areas were clearly separated by factor. In addition, the heritabilities of the extracted five factors were in the range of 8-24%. These estimates are in agreement with some previously published data. The heritabilities of the factors describing palmar asymmetry are slightly lower than those describing finger asymmetry. The present results support the hypothesis that both types of asymmetry have a genetic basis and are influenced by the intrauterine environment. 相似文献
126.
Karmakar S Ukil A Mukherjee S Das PK 《The international journal of biochemistry & cell biology》2006,38(8):1277-1289
A neuronal type Ca2+ stimulated nitric oxide synthase was earlier reported by us to be present in the protozoan parasite Leishmania donovani. As part of nitric oxide-cyclic GMP transduction signaling operative in higher eukaryotes and involved in the long-term potentiation, a soluble guanylyl cyclase has also been detected in this lower eukaryote. However, detailed biochemical characterization revealed the enzyme to be Ca2+ modulated and unstimulated by nitric oxide donors as opposed to higher eukaryotes. The possible role of intracellular Ca2+ level in the regulation of guanylyl cyclase activity as well as L. donovani infectivity was explored by measuring the intracellular survival of the parasites in mammalian macrophages after treatments, which decrease or elevate the intracellular Ca2+. Parasites loaded with intracellular Ca2+ chelators displayed significantly decreased infectivity and cyclic GMP level. In contrast, pretreatment with Ca2+ ionophores, which elevated Ca2+ levels in L. donovani, significantly enhanced the cyclic GMP level as well as the infectivity of the parasites. Moreover, treatment with selective inhibitors of soluble guanylyl cyclase also reduced infectivity, even in cases of calcium ionophore-treated parasites. The gene encoding the soluble guanylyl cyclase was cloned, sequenced and over expressed in bacterial system. The recombinant protein showed enzyme characteristics similar to that obtained in L. donovani promastigote cytosol. Together these results suggest a possible link between guanylyl cyclase, intracellular Ca2+ content and parasite infectivity. 相似文献
127.
Sean R. Stowell Moonjae Cho Christa L. Feasley Connie M. Arthur Xuezheng Song Jennifer K. Colucci Sougata Karmakar Padmaja Mehta Marcelo Dias-Baruffi Rodger P. McEver Richard D. Cummings 《The Journal of biological chemistry》2009,284(8):4989-4999
Galectin-1 (Gal-1) regulates leukocyte turnover by inducing the cell
surface exposure of phosphatidylserine (PS), a ligand that targets cells for
phagocytic removal, in the absence of apoptosis. Gal-1 monomer-dimer
equilibrium appears to modulate Gal-1-induced PS exposure, although the
mechanism underlying this regulation remains unclear. Here we show that
monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidation. A mutant
form of Gal-1, containing C2S and V5D mutations (mGal-1), exhibits impaired
dimerization and fails to induce cell surface PS exposure while retaining the
ability to recognize carbohydrates and signal Ca2+ flux in
leukocytes. mGal-1 also displayed enhanced sensitivity to oxidation, whereas
ligand, which partially protected Gal-1 from oxidation, enhanced Gal-1
dimerization. Continual incubation of leukocytes with Gal-1 resulted in
gradual oxidative inactivation with concomitant loss of cell surface PS,
whereas rapid oxidation prevented mGal-1 from inducing PS exposure.
Stabilization of Gal-1 or mGal-1 with iodoacetamide fully protected Gal-1 and
mGal-1 from oxidation. Alkylation-induced stabilization allowed Gal-1 to
signal sustained PS exposure in leukocytes and mGal-1 to signal both
Ca2+ flux and PS exposure. Taken together, these results
demonstrate that monomer-dimer equilibrium regulates Gal-1 sensitivity to
oxidative inactivation and provides a mechanism whereby ligand partially
protects Gal-1 from oxidation.Immunological homeostasis relies on efficient contraction of activated
leukocytes following an inflammatory episode. Several factors, including
members of the galectin and tumor necrosis factor families
(1,
2), regulate leukocyte turnover
by inducing apoptotic cell death. In contrast, several galectin family
members, in particular galectin-1
(Gal-1),2 uniquely
regulate neutrophil turnover by inducing phosphatidylserine (PS) exposure,
which normally sensitizes apoptotic cells to phagocytic removal
(3,
4), independent of apoptosis, a
process recently termed preaparesis
(5).Previous studies suggested that dimerization may be required for
Gal-1-induced PS exposure, as a mutant form of Gal-1 (mGal-1) containing two
point mutations within the dimer interface, C2S and V5D (C2S,V5D), displays
impaired Gal-1 dimerization and fails to induce PS exposure
(6). However, the manner in
which monomer-dimer equilibrium regulates Gal-1 signaling remains unclear.
Previous studies suggest that dimerization may be required for efficient
cross-linking of functional receptors or the formation of signaling lattices
(7–9).
Consistent with this, monomeric mutants of several other galectins fail to
induce PS exposure or signal leukocytes
(4,
8). Gal-1 signaling of PS
exposure requires initial signaling events, such as mobilization of
intracellular Ca2+ followed by sustained receptor engagement
(10). Although mGal-1 fails to
induce PS exposure (6), whether
mGal-1 can induce these initial signaling events remains unknown
(10).In addition to directly regulating signaling, monomer-dimer equilibrium may
also regulate other aspects of Gal-1 function. Unlike many other proteins
involved in the regulation of immunity, Gal-1 displays unique sensitivity to
oxidative inactivation
(11–15).
Although engagement of ligand partially protects Gal-1 from oxidation
(15), the impact of Gal-1
oxidation on signaling remains enigmatic. During oxidation, Gal-1 forms three
distinct intramolecular disulfide bridges that facilitate profound
conformational changes that preclude ligand binding and Gal-1 dimerization
(12–14),
suggesting that monomerdimer equilibrium may also regulate Gal-1 sensitivity
to oxidative inactivation.Previous studies utilized dithiothreitol (DTT) in treatment conditions to
protect Gal-1 from oxidative inactivation
(16,
17). Indeed, failure to
include DTT precluded Gal-1-induced death in T cells
(3,
18), suggesting that Gal-1
undergoes rapid oxidation in vivo in the absence of reducing
conditions. However, DTT itself can induce apoptosis in leukocytes
(19), leaving questions
regarding the impact of Gal-1 oxidation on these signaling events. In
contrast, recent studies utilizing iodoacetamide-alkylated Gal-1 (iGal-1),
previously shown to protect Gal-1 from oxidative inactivation
(20–29),
demonstrated that DTT actually primes cells to become sensitive to
Gal-1-induced apoptosis regardless of Gal-1 sensitivity to oxidation
(5).As the engagement of leukocyte ligands requires glycan recognition and
oxidation precludes this binding
(11,
15), understanding the impact
of oxidation on Gal-1 signals will facilitate a greater appreciation of the
factors that govern Gal-1 oxidation and therefore function. Our results
demonstrate that Gal-1 monomer-dimer equilibrium provides a key regulatory
point controlling both Gal-1 sensitivity to oxidation and its ability to
signal PS exposure in leukocytes. These results provide novel insights into
Gal-1 function and explain at a biochemical level the mechanisms regulating
Gal-1 oxidative inactivation and signaling. 相似文献
128.
Karmakar B Malkin I Kobyliansky E 《Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur》2012,69(2):221-228
Dermatoglyphic traits in a sample of twins were analyzed to estimate the resemblance between MZ and DZ twins and to evaluate the mode of inheritance by using the maximum likelihood-based Variance decomposition analysis. The additive genetic variance component was significant in both sexes for four traits--PII, AB_RC, RC_HB, and ATD_L. AB RC and RC_HB had significant sex differences in means, whereas PII and ATD_L did not. The results of the Bivariate Variance decomposition analysis revealed that PII and RC_HB have a significant correlation in both genetic and residual components. Significant correlation in the additive genetic variance between AB_RC and ATD_L was observed. The same analysis only for the females sub-sample in the three traits RBL, RBR and AB_DIS shows that the additive genetic RBR component was significant and the AB_DIS sibling component was not significant while others cannot be constrained to zero. The additive variance for AB DIS sibling component was not significant. The three components additive, sibling and residual were significantly correlated between each pair of traits revealed by the Bivariate Variance decomposition analysis. 相似文献
129.
C-di-GMP, a bacterial second messenger plays a key role in survival and adaptation of bacteria under different environmental conditions. The level of c-di-GMP is regulated by two opposing activities, namely diguanylate cyclase (DGC) and phosphodiesterase (PDE-A) exhibited by GGDEF and EAL domain, respectively in the same protein. Previously, we reported a bifunctional GGDEF-EAL domain protein, MSDGC-1 from Mycobacterium smegmatis showing both these activities (Kumar and Chatterji, 2008). In this current report, we have identified and characterized the homologous protein from Mycobacterium tuberculosis (Rv 1354c) named as MtbDGC. MtbDGC is also a bifunctional protein, which can synthesize and degrade c-di-GMP in vitro. Further we expressed Mtbdgc in M. smegmatis and it was able to complement the MSDGC-1 knock out strain by restoring the long term survival of M. smegmatis. Another protein Rv 1357c, named as MtbPDE, is an EAL domain protein and degrades c-di-GMP to pGpG in vitro. Rv1354c and 1357c have seven cysteine amino acids in their sequence, distributed along the full length of the protein. Disulfide bonds play an important role in stabilizing protein structure and regulating protein function. By proteolytic digestion and mass spectrometric analysis of MtbDGC, connectivity between cysteine pairs Cys94-Cys584, Cys2-Cys479 and Cys429-Cys614 was determined, whereas the third cysteine (Cys406) from N terminal was found to be free in MtbDGC protein, which was further confirmed by alkylation with iodoacetamide labeling. Bioinformatics modeling investigations also supported the pattern of disulfide connectivity obtained by Mass spectrometric analysis. Cys406 was mutated to serine by site directed mutagenesis and the mutant MtbC406S was not found to be active and was not able to synthesize or degrade c-di-GMP. The disulfide connectivity established here would help further in understanding the structure - function relationship in MtbDGC. 相似文献
130.
Sriram Tyagarajan Prasun K. Chakravarty Bishan Zhou Michael H. Fisher Mathew J. Wyvratt Kathy Lyons Tracy Klatt Xiaohua Li Sanjeev Kumar Brande Williams John Felix Birgit T. Priest Richard M. Brochu Vivien Warren McHardy Smith Maria Garcia Gregory J. Kaczorowski William J. Martin Catherine Abbadie Erin McGowan William H. Parsons 《Bioorganic & medicinal chemistry letters》2010,20(18):5536-5540
Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. With a goal to develop potent peripherally active sodium channel blockers, a series of low molecular weight biaryl substituted imidazoles, oxazoles, and thiazole carboxamides were identified with good in vitro and in vivo potency. 相似文献