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121.
Next‐generation sequencing for identification of candidate genes for Fusarium wilt and sterility mosaic disease in pigeonpea (Cajanus cajan) 下载免费PDF全文
Vikas K. Singh Aamir W. Khan Rachit K. Saxena Vinay Kumar Sandip M. Kale Pallavi Sinha Annapurna Chitikineni Lekha T. Pazhamala Vanika Garg Mamta Sharma Chanda Venkata Sameer Kumar Swathi Parupalli Suryanarayana Vechalapu Suyash Patil Sonnappa Muniswamy Anuradha Ghanta Kalinati Narasimhan Yamini Rajeev K. Varshney 《Plant biotechnology journal》2016,14(5):1183-1194
To map resistance genes for Fusarium wilt (FW) and sterility mosaic disease (SMD) in pigeonpea, sequencing‐based bulked segregant analysis (Seq‐BSA) was used. Resistant (R) and susceptible (S) bulks from the extreme recombinant inbred lines of ICPL 20096 × ICPL 332 were sequenced. Subsequently, SNP index was calculated between R‐ and S‐bulks with the help of draft genome sequence and reference‐guided assembly of ICPL 20096 (resistant parent). Seq‐BSA has provided seven candidate SNPs for FW and SMD resistance in pigeonpea. In parallel, four additional genotypes were re‐sequenced and their combined analysis with R‐ and S‐bulks has provided a total of 8362 nonsynonymous (ns) SNPs. Of 8362 nsSNPs, 60 were found within the 2‐Mb flanking regions of seven candidate SNPs identified through Seq‐BSA. Haplotype analysis narrowed down to eight nsSNPs in seven genes. These eight nsSNPs were further validated by re‐sequencing 11 genotypes that are resistant and susceptible to FW and SMD. This analysis revealed association of four candidate nsSNPs in four genes with FW resistance and four candidate nsSNPs in three genes with SMD resistance. Further, In silico protein analysis and expression profiling identified two most promising candidate genes namely C.cajan_01839 for SMD resistance and C.cajan_03203 for FW resistance. Identified candidate genomic regions/SNPs will be useful for genomics‐assisted breeding in pigeonpea. 相似文献
122.
The purpose of this study was to improve the aqueous solubility, dissolution, and pharmacodynamic properties of a BCS class II drug, ezetimibe (Eze) by preparing ternary cyclodextrin complex systems. We investigated the potential synergistic effect of two novel hydrophilic auxiliary substances, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and l-ascorbic acid-2-glucoside (AA2G) on hydroxypropyl-β-cyclodextrin (HPBCD) solubilization of poorly water-soluble hypocholesterolemic drug, Eze. In solution state, the binary and ternary systems were analyzed by phase solubility studies and Job’s plot. The solid complexes prepared by freeze-drying were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and scanning electron microscopy (SEM). The log P values, aqueous solubility, dissolution, and antihypercholesterolemic activity of all systems were studied. The analytical techniques confirmed the formation of inclusion complexes in the binary and ternary systems. HPBCD complexation significantly (p?<?0.05) reduced the log P and improved the solubility, dissolution, and hypocholesterolemic properties of Eze, and the addition of ternary component produced further significant improvement (p?<?0.05) even compared to binary system. The remarkable reduction in log P and enhancement in solubility, dissolution, and antihypercholesterolemic activity due to the addition of TPGS or AA2G may be attributed to enhanced wetting, dispersibility, and complete amorphization. The use of TPGS or AA2G as ternary hydrophilic auxiliary substances improved the HPBCD solubilization and antihypercholesterolemic activity of Eze. 相似文献
123.
124.
A simple procedure for the preparation of agarose suitable for electrophoresis is developed in which anionic polysaccharides are removed by extracting the agar gel-granules with phosphate buffer (0.03 M, pH 6.8) containing urea (4 M), followed by electrophoresis in the same buffer system. Further, alkali treatment in the presence of sodium borohydride, eliminates electroendosmosis, giving essentially a neutral agarose, as judged by the electrophoretic behaviour of basic substances like crystal violet and cytochrome C. The purified agarose with yields 60-65%, has a sulphur content less than 0.1%, and forms rigid, transparent gels. 相似文献
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Michael C. Dyle Scott M. Ebert Daniel P. Cook Steven D. Kunkel Daniel K. Fox Kale S. Bongers Steven A. Bullard Jason M. Dierdorff Christopher M. Adams 《The Journal of biological chemistry》2014,289(21):14913-14924
Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy. 相似文献
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Bertha C. Elias Takuya Suzuki Ankur Seth Francesco Giorgianni Gautam Kale Le Shen Jerrold R. Turner Anjaparavanda Naren Dominic M. Desiderio Radhakrishna Rao 《The Journal of biological chemistry》2009,284(3):1559-1569
Occludin is phosphorylated on tyrosine residues during the oxidative
stress-induced disruption of tight junction, and in vitro
phosphorylation of occludin by c-Src attenuates its binding to ZO-1. In the
present study mass spectrometric analyses of C-terminal domain of occludin
identified Tyr-379 and Tyr-383 in chicken occludin as the phosphorylation
sites, which are located in a highly conserved sequence of occludin, YETDYTT;
Tyr-398 and Tyr-402 are the corresponding residues in human occludin. Deletion
of YETDYTT motif abolished the c-Src-mediated phosphorylation of occludin and
the regulation of ZO-1 binding. Y398A and Y402A mutations in human occludin
also abolished the c-Src-mediated phosphorylation and regulation of ZO-1
binding. Y398D/Y402D mutation resulted in a dramatic reduction in ZO-1 binding
even in the absence of c-Src. Similar to wild type occludin, its Y398A/Y402A
mutant was localized at the plasma membrane and cell-cell contact sites in
Rat-1 cells. However, Y398D/Y402D mutants of occludin failed to localize at
the cell-cell contacts. Calcium-induced reassembly of Y398D/Y402D mutant
occludin in Madin-Darby canine kidney cells was significantly delayed compared
with that of wild type occludin or its T398A/T402A mutant. Furthermore,
expression of Y398D/Y402D mutant of occludin sensitized MDCK cells for
hydrogen peroxide-induced barrier disruption. This study reveals a unique
motif in the occludin sequence that is involved in the regulation of ZO-1
binding by reversible phosphorylation of specific Tyr residues.Epithelial tight junctions
(TJs)2 form a
selective barrier to the diffusion of toxins, allergens, and pathogens from
the external environment into the tissues in the gastrointestinal tract, lung,
liver, and kidney (1).
Disruption of TJs is associated with the gastrointestinal diseases such as
inflammatory bowel disease, celiac disease, infectious enterocolitis, and
colon cancer
(2–4)
as well as in diseases of lung and kidney
(5,
6). Numerous inflammatory
mediators such as tumor necrosis factor α, interferon γ, and
oxidative stress
(7–12)
are known to disrupt the epithelial TJs and the barrier function. Several
studies have indicated that hydrogen peroxide disrupts the TJs in intestinal
epithelium by a tyrosine kinase-dependent mechanism
(11,
12).Four types of integral proteins, occludin, claudins, junctional adhesion
molecules, and tricellulin are associated with TJs. Occludin, claudins, and
tricellulin are tetraspan proteins, and their extracellular domains interact
with homotypic domains of the adjacent cells
(1,
2,
13). The intracellular domains
of these proteins interact with a variety of soluble proteins such as ZO-1,
ZO-2, ZO-3, 7H6, cingulin, and symplekin
(14–23);
this protein complex interacts with the perijunctional actomyosin ring. The
interactions among TJ proteins are essential for the assembly and the
maintenance of TJs. Therefore, regulation of the interactions among TJ
proteins may regulate the TJ integrity. A significant body of evidence
indicates that numerous signaling molecules are associated with the TJs.
Protein kinases and protein phosphatases such as protein kinase Cζ
(PKCζ), PKCι/λ
(24), c-Src
(25), c-Yes
(26,
27), mitogen-activated protein
kinase (28), PP2A, and PP1
(29) interact with TJs,
indicating that TJs are dynamically regulated by intracellular signal
transduction involving protein phosphorylation. Additionally, other signaling
molecules such as calcium
(30), phosphatidylinositol
3-kinase (31), Rho
(32), and Rac
(33) are involved in the
regulation of TJs.Occludin, a ∼65-kDa protein, has been well characterized to be
assembled into the TJs. Although occludin knock-out mice showed the formation
of intact TJs in different epithelia
(34), numerous studies have
emphasized that it plays an important role in the regulation of TJ integrity.
Occludin spans the membrane four times to form two extracellular loops and one
intracellular loop, and the N-terminal and C-terminal domains hang into the
intracellular compartment
(35–37).
In epithelium with intact TJs, occludin is highly phosphorylated on Ser and
Thr residues (38), whereas Tyr
phosphorylation is undetectable. However, the disruption of TJs in Caco-2 cell
monolayers by oxidative stress and acetaldehyde leads to Tyr phosphorylation
of occludin; the tyrosine kinase inhibitors attenuate the disruption of TJs
(39,
40). Furthermore, a previous
in vitro study demonstrated that Tyr phosphorylation of the
C-terminal domain of occludin leads to the loss of its interaction with ZO-1
and ZO-3 (25).In the present study we identified the Tyr residues in occludin that are
phosphorylated by c-Src and determined their role in regulated interaction
between occludin and ZO-1 and its assembly into the TJs. Results show that 1)
Tyr-379 and Tyr-383 in chicken occludin and Tyr-398 and Tyr-402 in human
occludin are the exclusive sites of phosphorylation by c-Src, and these Tyr
residues are located in a highly conserved sequence of occludin, YET-DYTT, 2)
deletion of YEDTYTT or point mutation of Tyr-398 and Tyr-402 in human occludin
attenuates the phosphorylation-dependent regulation of ZO-1 binding, 3)
Y398D/Y402D mutation of human occludin leads to loss of ZO-1 binding and
prevents its translocation to the plasma membrane and cell-cell contact sites
in Rat-1 cells, 4) Y398D/Y402D mutation of occludin delays its assembly into
the intercellular junctions during the calcium-induced assembly of TJs, and 5)
expression of Y398D/Y402D mutant occludin sensitizes cell monolayers for
hydrogen peroxide-induced disruption of barrier function. 相似文献
130.
Cooperativity is extensively used by enzymes, particularly those acting at key metabolic branch points, to “fine tune” catalysis. Thus, cooperativity and enzyme catalysis are intimately linked, yet their linkage is poorly understood. Here we show that negative cooperativity in the rate-determining step in the E1 component of the Escherichia coli pyruvate dehydrogenase multienzyme complex is an outcome of redistribution of a “rate-promoting” conformational pre-equilibrium. An array of biophysical and biochemical studies indicates that non-catalytic but conserved residues directly regulate the redistribution. Furthermore, factors such as ligands and temperature, individually or in concert, also strongly influence the redistribution. As a consequence, these factors also exert their influence on catalysis by profoundly influencing the pre-equilibrium facilitated dynamics of communication between multienzyme components. Our observations suggest a mode of cooperativity in the E1 component that is consistent with the dynamical hypothesis shown to satisfactorily explain cooperativity in many well studied enzymes. The results point to the likely existence of multiple modes of communication between subunits when the entire class of thiamin diphosphate-dependent enzymes is considered. 相似文献