The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP.

abstract：:The Pleistocene global dispersal of modern humans required the transit of arid and semiarid regions where the distribution of potable water provided a primary constraint on dispersal pathways. Here, we provide a spatially explicit continental-scale assessment of the opportunities for Pleistocene human occupation of Au...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Bird MI,O'Grady D,Ulm S

更新日期：2016-10-11 00:00:00

abstract：:A critical step in the induction of apoptosis is the activation of the apoptotic initiator caspase 9. We show that at its normal physiological concentration, caspase 9 is primarily an inactive monomer (zymogen), and that activity is associated with a dimeric species. At the high concentrations used for crystal formati...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Renatus M,Stennicke HR,Scott FL,Liddington RC,Salvesen GS

更新日期：2001-12-04 00:00:00

abstract：:Vaccination is the most effective medical intervention ever introduced and, together with clean water and sanitation, it has eliminated a large part of the infectious diseases that once killed millions of people. A recent study concluded that since 1924 in the United States alone, vaccines have prevented 40 million ca...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Rappuoli R,Pizza M,Del Giudice G,De Gregorio E

更新日期：2014-08-26 00:00:00

abstract：:Tissue factor (TF) plays an important role in hemostasis, inflammation, angiogenesis, and the pathophysiology of atherosclerosis and cancer. In this article we uncover a mechanism in which protein S, which is well known as the cofactor of activated protein C, specifically inhibits TF activity by promoting the interact...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Hackeng TM,Seré KM,Tans G,Rosing J

更新日期：2006-02-28 00:00:00

abstract：:The oligopeptide permease of Escherichia coli has been characterized by Payne, Gilvarg, and their colleagues. We have confirmed its existence in Salmonella typhimurium, and have isolated a series of mutants lacking the permease. We use this transport system for smuggling a histidine biosynthetic intermediate, histidin...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Ames BN,Ames GF,Young JD,Tsuchiya D,Lecocq J

更新日期：1973-02-01 00:00:00

abstract：:The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Miller LM,Recanzone GH

更新日期：2009-04-07 00:00:00

abstract：:Dematerialization, represented by declining consumption per GDP of energy or of goods, offers some hope for rising environmental quality with development. The declining proportion of income spent on staples as affluence grows, which income elasticity <1.0 measures, makes dematerialization widespread. Further, as learn...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Ausubel JH,Waggoner PE

更新日期：2008-09-02 00:00:00

abstract：:We provide evidence that citrate anions bridge between mineral platelets in bone and hypothesize that their presence acts to maintain separate platelets with disordered regions between them rather than gradual transformations into larger, more ordered blocks of mineral. To assess this hypothesis, we take as a model fo...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Davies E,Müller KH,Wong WC,Pickard CJ,Reid DG,Skepper JN,Duer MJ

更新日期：2014-04-08 00:00:00

abstract：:Throughout three domains of life, alanyl-tRNA synthetases (AlaRSs) recognize a G3:U70 base pair in the acceptor stem of tRNAAla as the major identity determinant of tRNAAla The crystal structure of the archaeon Archaeoglobus fulgidus AlaRS in complex with tRNAAla provided the basis for G3:U70 recognition with residues...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Chong YE,Guo M,Yang XL,Kuhle B,Naganuma M,Sekine SI,Yokoyama S,Schimmel P

更新日期：2018-07-17 00:00:00

abstract：:The cis-acting regulatory sequence of transcription from long terminal repeats (LTRs) of human T-cell leukemia virus type I and type II (HTLV-I and HTLV-II), which is essential for action of the virally encoded trans-acting transcriptional factor(s) designated pX(s), in HTLV-I and -II was identified. Deletion of most ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Shimotohno K,Takano M,Teruuchi T,Miwa M

更新日期：1986-11-01 00:00:00

abstract：:CD4(+) T cells producing IL-17 [T helper (Th)17], as distinct from Th1 or Th2 cells, have recently been shown to be associated with autoimmunity, but it is not entirely clear how Th17 cells are generated from naïve T cells. We demonstrate here that IL-6, but not TNF-alpha or IL-1beta, can, in combination with TGF-beta...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kimura A,Naka T,Kishimoto T

更新日期：2007-07-17 00:00:00

abstract：:One of the serious limitations of tokamaks as reactors is the occurrence of disruptions. Stellarators designed by advanced computational methods provide an attractive alternative for a major experiment in magnetic fusion research. Configurations with approximate two-dimensional magnetic symmetry have been found with h...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Garabedian PR

更新日期：2000-02-01 00:00:00

abstract：:The marine nitrogen fixing microorganisms (diazotrophs) are a major source of nitrogen to open ocean ecosystems and are predicted to be limited by iron in most marine environments. Here we use global and targeted proteomic analyses on a key unicellular marine diazotroph Crocosphaera watsonii to reveal large scale diel...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Saito MA,Bertrand EM,Dutkiewicz S,Bulygin VV,Moran DM,Monteiro FM,Follows MJ,Valois FW,Waterbury JB

更新日期：2011-02-08 00:00:00

abstract：:Small proteins can fold remarkably rapidly, even in μs. What limits their rate of folding? The Engrailed homeodomain is a particularly well-characterized example, which folds ultrafast via an intermediate, I, of solved structure. It is a puzzle that the helix2-turn-helix3 motif of the 3-helix bundle forms in approxima...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Neuweiler H,Banachewicz W,Fersht AR

更新日期：2010-12-21 00:00:00

abstract：:In suspension cultures of mouse spleen cells, the addition of small amounts (1-100 ng) of a heterologous antigen to which the donor mice had been primed significantly increased the number of anti-sheep erythrocyte plaques appearing after stimulation with sheep erythrocytes. A similar addition to identical cultures fro...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Rubin AS,Coons AH

更新日期：1971-08-01 00:00:00

abstract：:Most proteins are in equilibrium with partially and globally unfolded conformations. In contrast, kinetically stable proteins (KSPs) are trapped by an energy barrier in a specific state, unable to transiently sample other conformations. Among many potential roles, it appears that kinetic stability (KS) is a feature us...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Xia K,Manning M,Hesham H,Lin Q,Bystroff C,Colón W

更新日期：2007-10-30 00:00:00

abstract：:Previous research has implicated a large network of brain regions in the processing of risk during decision making. However, it has not yet been determined if activity in these regions is predictive of choices on future risky decisions. Here, we examined functional MRI data from a large sample of healthy subjects perf...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Helfinstein SM,Schonberg T,Congdon E,Karlsgodt KH,Mumford JA,Sabb FW,Cannon TD,London ED,Bilder RM,Poldrack RA

更新日期：2014-02-18 00:00:00

abstract：:In multicellular organisms, the higher order organization of chromatin during interphase and the reassembly of the nuclear envelope during mitosis are thought to involve an interaction between the nuclear lamina and chromatin. The nuclear distribution of lamins and of peripheral chromatin is highly correlated in vivo,...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Goldberg M,Harel A,Brandeis M,Rechsteiner T,Richmond TJ,Weiss AM,Gruenbaum Y

更新日期：1999-03-16 00:00:00

abstract：:Although it is now more than two decades since it was first reported that the imidazobenzodiazepine Ro15-4513 reverses behavioral alcohol effects, the molecular target(s) of Ro15-4513 and the mechanism of alcohol antagonism remain elusive. Here, we show that Ro15-4513 blocks the alcohol enhancement on recombinant "ext...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Wallner M,Hanchar HJ,Olsen RW

更新日期：2006-05-30 00:00:00

abstract：:The amino-terminal 20 amino acids are required for microinjected ribonuclease A (RNase A) to be taken up by lysosomes and degraded at an enhanced rate during serum withdrawal. We used water-soluble carbodiimides to covalently attach the RNase S-peptide (residues 1-20) to [3H]RNase S-protein (residues 21-124) at unspec...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Backer JM,Dice JF

更新日期：1986-08-01 00:00:00

abstract：:The frequency of recombination between the G gamma-globin (HBG2) and parathyroid hormone (PTH) loci on the short arm of human chromosome 11 was estimated by typing greater than 700 single-sperm samples from two males. The sperm-typing technique employed involves the polymerase chain reaction and allele-specific oligon...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Cui XF,Li HH,Goradia TM,Lange K,Kazazian HH Jr,Galas D,Arnheim N

更新日期：1989-12-01 00:00:00

abstract：:The glycosyltransferases of the mammalian Golgi complex must recycle between the stacked cisternae of that organelle to maintain their proper steady-state localization. This trafficking is mediated by COPI-coated vesicles, but how the glycosyltransferases are incorporated into these transport vesicles is poorly unders...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Liu L,Doray B,Kornfeld S

更新日期：2018-09-04 00:00:00

abstract：:The three-dimensional structure of alpha-cobra-toxin, the "long" neurotoxin from the venom of Naja naja siamensis, has been determined at 2.8-A resolution. Crystals grown as hexagonal needles have space group P6522 with unit cell parameters a = b = 74.59 A, c = 42.89 A; one molecule per asymmetric unit. Phases were de...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Walkinshaw MD,Saenger W,Maelicke A

更新日期：1980-05-01 00:00:00

abstract：:A 24-amino acid residue peptide has been isolated from the Fc region of a human IgG1 myeloma protein. The peptide has associated with it the same ability to induce murine B cells to polyclonally secrete antibody as does the intact Fc fragment. Amino acid composition of the peptide indicates that on a mole/mole basis t...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Morgan EL,Hugli TE,Weigle WO

更新日期：1982-09-01 00:00:00

abstract：:DNA mismatch repair is central to the maintenance of genomic stability. It is initiated by the recognition of base-base mismatches and insertion/deletion loops by the family of MutS proteins. Subsequently, ATP induces a unique conformational change in the MutS-mismatch complex but not in the MutS-homoduplex complex th...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Wang H,Yang Y,Schofield MJ,Du C,Fridman Y,Lee SD,Larson ED,Drummond JT,Alani E,Hsieh P,Erie DA

更新日期：2003-12-09 00:00:00

abstract：:Deuterium oxide, D(2)O, increases the temperature-tolerance of Drosophila pseudoobscura when it is administered to adult flies as a sucrose solution. The effect is very rapidly exerted; it is detected within 10 min after the flies have a brief (10 min) opportunity to drink. This increased resistance to heat-death sure...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Pittendrigh CS,Cosbey ES

更新日期：1974-02-01 00:00:00

abstract：:The phosphatidylinositol 3-kinase subunit PIK3CA is frequently mutated in human cancers. Here we used gene targeting to "knock in" PIK3CA mutations into human breast epithelial cells to identify new therapeutic targets associated with oncogenic PIK3CA. Mutant PIK3CA knockin cells were capable of epidermal growth facto...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Gustin JP,Karakas B,Weiss MB,Abukhdeir AM,Lauring J,Garay JP,Cosgrove D,Tamaki A,Konishi H,Konishi Y,Mohseni M,Wang G,Rosen DM,Denmeade SR,Higgins MJ,Vitolo MI,Bachman KE,Park BH

更新日期：2009-02-24 00:00:00

abstract：:Dihydroisohistrionicotoxin inhibits acetylcholine receptor-dependent 22Na+ uptake of cultured chick muscle cells with a KI of 0.2 micrometer. The inhibition is noncompetitive with respect to agonists. The toxin enhances desensitization of the receptor by agonists which is accompanied by a 10-fold increase in receptor ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Burgermeister W,Catterall WA,Witkop B

更新日期：1977-12-01 00:00:00

abstract：:A method for estimating intrafamilial correlations under variable family sizes involving weightings of paired data points is introduced. Classical methods of intrafamilial correlation estimation and those in current use are outlined and critically analyzed. Extensions of the proposed estimation method to more general ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Karlin S,Cameron EC,Williams PT

更新日期：1981-05-01 00:00:00

abstract：:A five-helix secondary structural model is proposed for eukaryotic cytoplasmic 5S rRNA. All available sequence data are consistent with this model including those from Chlorella 5S rRNA whose sequence is revised by data included here. Various architectural features of eukaryotic 5S rRNA are summarized in terms of this...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Luehrsen KR,Fox GE

更新日期：1981-04-01 00:00:00