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排序方式: 共有196条查询结果,搜索用时 15 毫秒
31.
Genome‐wide identification of miR‐200 targets reveals a regulatory network controlling cell invasion
Cameron P Bracken Xiaochun Li Josephine A Wright David M Lawrence Katherine A Pillman Marika Salmanidis Matthew A Anderson B Kate Dredge Philip A Gregory Anna Tsykin Corine Neilsen Daniel W Thomson Andrew G Bert Joanne M Leerberg Alpha S Yap Kirk B Jensen Gregory J Goodall 《The EMBO journal》2014,33(18):2040-2056
32.
Jonathan E. Ulmer Eric Morssing Vilén Ramesh Babu Namburi Alhosna Benjdia Julie Beneteau Annie Malleron David Bonnaffé Pierre-Alexandre Driguez Karine Descroix Gilbert Lassalle Christine Le Narvor Corine Sandstr?m Dorothe Spillmann Olivier Berteau 《The Journal of biological chemistry》2014,289(35):24289-24303
Despite the importance of the microbiota in human physiology, the molecular bases that govern the interactions between these commensal bacteria and their host remain poorly understood. We recently reported that sulfatases play a key role in the adaptation of a major human commensal bacterium, Bacteroides thetaiotaomicron, to its host (Benjdia, A., Martens, E. C., Gordon, J. I., and Berteau, O. (2011) J. Biol. Chem. 286, 25973–25982). We hypothesized that sulfatases are instrumental for this bacterium, and related Bacteroides species, to metabolize highly sulfated glycans (i.e. mucins and glycosaminoglycans (GAGs)) and to colonize the intestinal mucosal layer. Based on our previous study, we investigated 10 sulfatase genes induced in the presence of host glycans. Biochemical characterization of these potential sulfatases allowed the identification of GAG-specific sulfatases selective for the type of saccharide residue and the attachment position of the sulfate group. Although some GAG-specific bacterial sulfatase activities have been described in the literature, we report here for the first time the identity and the biochemical characterization of four GAG-specific sulfatases. Furthermore, contrary to the current paradigm, we discovered that B. thetaiotaomicron possesses an authentic GAG endosulfatase that is active at the polymer level. This type of sulfatase is the first one to be identified in a bacterium. Our study thus demonstrates that bacteria have evolved more sophisticated and diverse GAG sulfatases than anticipated and establishes how B. thetaiotaomicron, and other major human commensal bacteria, can metabolize and potentially tailor complex host glycans. 相似文献
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Jean-Alain Fehrentz Corine Genu-Dellac Muriel Amblard Franclois Winternitz Albert Loffet Jean Martinez 《Journal of peptide science》1995,1(2):124-131
N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected β amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerially pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced (4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodol]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields. 相似文献
34.
L.?C.?Coates D.?D.?Gladman P.?Nash O.?FitzGerald A.?Kavanaugh T.?K.?Kvien L.?Gossec V.?Strand L.?Rasouliyan L.?Pricop K.?Ding S.?M.?Jugl C.?Gaillez 《Arthritis research & therapy》2018,20(1):272
Background
Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2?years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2?years among patients with PsA in the FUTURE 2 study.Methods
PASDAS (cut-off scores: remission ≤?1.9; LDA >?1.9 and?<?3.2; Moderate Disease Activity ≥?3.2 and?<?5.4; and high disease activity [HDA]?≥?5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150?mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures.Results
In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300?mg and in 15.2% and 19.2%, respectively, in the secukinumab 150?mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission?+?LDA at week 16 with secukinumab 300 and 150?mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2?years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2?years.Conclusions
Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2?years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA.Trial registration
ClinicalTrials.gov, NCT01752634. Registered on December 19, 2012.EUDRACT, 2012-004439-22. Registered on December 12, 2012.35.
Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis 总被引:9,自引:0,他引:9
Camps M Rückle T Ji H Ardissone V Rintelen F Shaw J Ferrandi C Chabert C Gillieron C Françon B Martin T Gretener D Perrin D Leroy D Vitte PA Hirsch E Wymann MP Cirillo R Schwarz MK Rommel C 《Nature medicine》2005,11(9):936-943
Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis. 相似文献
36.
Depth‐based differentiation in nitrogen uptake between graminoids and shrubs in an Arctic tundra plant community 下载免费PDF全文
Peng Wang Juul Limpens Ake Nauta Corine van Huissteden Sophie Quirina van Rijssel Liesje Mommer Hans de Kroon Trofim C. Maximov Monique M.P.D. Heijmans 《植被学杂志》2018,29(1):34-41
Questions
The rapid climate warming in tundra ecosystems can increase nutrient availability in the soil, which may initiate shifts in vegetation composition. The direction in which the vegetation shifts will co‐determine whether Arctic warming is mitigated or accelerated, making the understanding of successional trajectories urgent. One of the key factors influencing the competitive relationships between plant species is their access to nutrients, depending on the depth where they take up most nutrients. However, nutrient uptake at different soil depths by tundra plant species that differ in rooting depth is unclear.Location
Kytalyk Nature Reserve, northeast Siberia, Russia.Methods
We injected 15N to 5 cm, 15 cm and the thaw front of the soil in a moist tussock tundra. The absorption of 15N by grasses, sedges, deciduous shrubs and evergreen shrubs from the three depths was compared.Results
The results clearly show a vertical differentiation of N uptake by these plant functional types, corresponding to their rooting strategy. Shallow‐rooting dwarf shrubs were more capable of absorbing nutrients from the upper soil than from deeper soil. Deep‐rooting grasses and sedges were more capable of absorbing nutrients from deeper soil than the dwarf shrubs. The natural 15N abundances in control plants also indicate that graminoids can absorb more nutrients from the deeper soil than dwarf shrubs.Conclusions
Our results show that graminoids and shrubs in the Arctic differ in their N uptake strategies, with graminoids profiting from nutrients released at the thaw front, while shrubs mainly forage in upper soil layers. Our results suggest that tundra vegetation will become graminoid‐dominated as permafrost thaw progresses and nutrient availability increases in the deep soil. 相似文献37.
A new subfamily of KH-domain-containing RNA-binding proteins is encoded by genes that are conserved from yeast to humans. Mutations with interesting developmental phenotypes have been identified in Caemorbabditis elegans, Drosophila and mouse. It is hypothesized that these bifunctional proteins provide a rich source of interesting molecular information about development and define a new cellular pathway that links signal transduction directly to RNA metabolism. 相似文献
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40.
Josef S. Smolen Jürgen Wollenhaupt Juan J. Gomez-Reino Walter Grassi Corine Gaillez Coralie Poncet Manuela Le Bars Rene Westhovens 《Arthritis research & therapy》2015,17(1)
IntroductionThis study evaluated various remission criteria in abatacept plus methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). We aimed to investigate the time to, and sustainability of, remission, and to evaluate the relationship between remission, function and structure.MethodsPost hoc analyses were performed from the 12-month, double-blind period of the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE) in patients with early RA (≤2 years) and poor prognostic factors, comparing abatacept plus MTX (n = 210) versus MTX alone (n = 209).ResultsAt month 12, Disease Activity Score 28, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index and Boolean remission rates were, for abatacept plus MTX versus MTX alone: 47.6 % versus 27.3 %, 33.3 % versus 12.4 %, 34.3 % versus 16.3 %, and 23.8 % versus 5.7 %, respectively. Cumulative probability demonstrated higher proportions achieving first remission and first sustained remission for abatacept plus MTX versus MTX alone (e.g., 23.3 % [95 % confidence interval (CI): 17.6, 29.1] vs 12.9 % [8.4, 17.5] for first SDAI remission over 0–6 months). For patients in SDAI remission at month 3, mean Health Assessment Questionnaire-Disability Index at month 12 was 0.20 versus 0.50 for abatacept plus MTX versus MTX alone. Mean changes in radiographic score from baseline to month 12 were minimal for patients in SDAI remission at month 3 in both groups, while less structural damage progression was seen, 0.75 versus 1.35, respectively, for abatacept plus MTX versus MTX alone for patients with moderate/high disease activity at month 3 (adjusted mean treatment difference: −0.60 [95 % CI: −1.11, −0.09; P < 0.05]).ConclusionsHigh proportions of abatacept plus MTX-treated patients achieved stringent remission criteria. Remission was associated with long-term functional benefit; dissociation was seen between clinical and structural outcomes for abatacept. These findings highlight the impact of reaching stringent remission targets early, on physical function and structural damage, in MTX-naïve biologic-treated patients.