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排序方式: 共有643条查询结果,搜索用时 15 毫秒
111.
112.
Amann M Friedrich M Lutterbuese P Vieser E Lorenczewski G Petersen L Brischwein K Kufer P Kischel R Baeuerle PA Schlereth B 《Cancer immunology, immunotherapy : CII》2009,58(1):95-109
MuS110 is a BiTE antibody bispecific for murine EpCAM (CD326) and murine CD3. A recent study has shown that muS110 has significant
anti tumor activity at well-tolerated doses as low as 5 μg/kg in orthotopic breast and lung cancer models (Amann et al. in
Cancer Res 68:143–151, 2008). Here, we have explored the safety profile of muS110 at higher doses. Escalation to 50 μg/kg muS110 caused in mice transient
loss of body weight, and transient piloerection, hypomotility, hypothermia and diarrhoea. These clinical signs coincided with
serum peaks of TNF-α, IL-6, IL-2, IFN-γ and IL-4, and an increase of surface markers for T cell activation. Because activation
of T cells in response to BiTE antibodies is typically dependent on target cells, we analyzed mouse blood for the presence
of EpCAM+ cells. Various mouse strains presented with a subpopulation of 2–3% EpCAM+ blood cells, mostly B and T lymphocytes, which was not detected in human blood samples. In vitro experiments in which the
number of EpCAM+ cells in blood samples was either reduced or increased suggested that both T cell activation and cytokine release in response
to muS110 was dependent on the number of target-expressing cells. In support for a role of EpCAM+ lymphocytes in the observed side effects, reduction of EpCAM+ blood cells in mice via a low-dose pre treatment with muS110 dramatically increased the tolerability of animals up to at
least 500 μg/kg of the BiTE antibody. This high tolerability to muS110 occurred in the presence of non-compromised T cells.
No damage to EpCAM+ epithelial tissues was evident from histopathological examination of animals daily injected with 100 μg/kg muS110 for 28 days.
In summary, these observations suggest that side effects of muS110 in mice were largely caused by an acute T cell activation
that was triggered by a subpopulation of EpCAM+ lymphocytes. Because humans have extremely low numbers of EpCAM+ cells in blood, this toxicity of an EpCAM-specific BiTE may be specific for mice.
M. Amann and M. Friedrich contributed equally to this work. 相似文献
113.
Anne‐Sophie Rivier Guillaume A. Castillon Laetitia Michon Masayoshi Fukasawa Maria Romanova‐Michaelides Nina Jaensch Kentaro Hanada Reika Watanabe 《Traffic (Copenhagen, Denmark)》2010,11(8):1017-1033
Previous studies have shown that yeast glycosylphosphatidylinositol‐anchored proteins (GPI‐APs) and other secretory proteins are preferentially incorporated into distinct coat protein II (COPII) vesicle populations for their transport from the endoplasmic reticulum (ER) to the Golgi apparatus, and that incorporation of yeast GPI‐APs into COPII vesicles requires specific lipid interactions. We compared the ER exit mechanism and segregation of GPI‐APs from other secretory proteins in mammalian and yeast cells. We find that, unlike yeast, ER‐to‐Golgi transport of GPI‐APs in mammalian cells does not depend on sphingolipid synthesis. Whereas ER exit of GPI‐APs is tightly dependent on Sar1 in mammalian cells, it is much less so in yeast. Furthermore, in mammalian cells, GPI‐APs and other secretory proteins are not segregated upon COPII vesicle formation, in contrast to the remarkable segregation seen in yeast. These findings suggest that GPI‐APs use different mechanisms to concentrate in COPII vesicles in the two organisms, and the difference might explain their propensity to segregate from other secretory proteins upon ER exit. 相似文献
114.
Bichara M Attmane-Elakeb A Brown D Essig M Karim Z Muffat-Joly M Micheli L Eude-Le Parco I Cluzeaud F Peuchmaur M Bonvalet JP Poirier F Farman N 《Glycobiology》2006,16(1):36-45
Galectin 3 belongs to a family of glycoconjugate-binding proteinsthat participate in cellular homeostasis by modulating cellgrowth, adhesion, and signaling. We studied adult galectin 3null mutant (Gal 3/) and wild-type (WT) mice togain insights into the role of galectin 3 in the kidney. Byimmunofluorescence, galectin 3 was found in collecting duct(CD) principal and intercalated cells in some regions of thekidney, as well as in the thick ascending limbs at lower levels.Compared to WT mice, Gal 3/ mice had ~11% fewerglomeruli (p < 0.04), associated with kidney hypertrophy(p < 0.006). In clearance experiments, urinary chloride excretionwas found to be higher in Gal 3/ than in WT mice(p < 0.04), but there was no difference in urinary bicarbonateexcretion, in glomerular filtration, or urinary flow rates.Under chronic low sodium diet, Gal 3/ mice hadlower extracellular fluid (ECF) volume than WT mice (p <0.05). Plasma aldosterone concentration was higher in Gal 3/than in WT mice (p < 0.04), which probably caused the observedincrease in -epithelial sodium channel (-ENaC) protein abundancein the mutant mice (p < 0.001). Chronic high sodium dietresulted paradoxically in lower blood pressure (p < 0.01)in Gal 3/ than in WT. We conclude that Gal 3/mice have mild renal chloride loss, which causes chronic ECFvolume contraction and reduced blood pressure levels. 相似文献
115.
Canini L Andréoletti L Ferrari P D'Angelo R Blanchon T Lemaitre M Filleul L Ferry JP Desmaizieres M Smadja S Valleron AJ Carrat F 《PloS one》2010,5(11):e13998
Background
Facemasks and respirators have been stockpiled during pandemic preparedness. However, data on their effectiveness for limiting transmission are scarce. We evaluated the effectiveness of facemask use by index cases for limiting influenza transmission by large droplets produced during coughing in households.Methodology and Principal Findings
A cluster randomized intervention trial was conducted in France during the 2008–2009 influenza season. Households were recruited during a medical visit of a household member with a positive rapid influenza A test and symptoms lasting less than 48 hours. Households were randomized either to the mask or control group for 7 days. In the intervention arm, the index case had to wear a surgical mask from the medical visit and for a period of 5 days. The trial was initially intended to include 372 households but was prematurely interrupted after the inclusion of 105 households (306 contacts) following the advice of an independent steering committee. We used generalized estimating equations to test the association between the intervention and the proportion of household contacts who developed an influenza-like illness during the 7 days following the inclusion. Influenza-like illness was reported in 24/148 (16.2%) of the contacts in the intervention arm and in 25/158 (15.8%) of the contacts in the control arm and the difference between arms was 0.40% (95%CI: −10% to 11%, P = 1.00). We observed a good adherence to the intervention. In various sensitivity analyses, we did not identify any trend in the results suggesting effectiveness of facemasks.Conclusion
This study should be interpreted with caution since the lack of statistical power prevents us to draw formal conclusion regarding effectiveness of facemasks in the context of a seasonal epidemic.Trial Registration
clinicaltrials.gov NCT00774774相似文献116.
Marine Jeanmougin Aurelien de Reynies Laetitia Marisa Caroline Paccard Gregory Nuel Mickael Guedj 《PloS one》2010,5(9)
High-throughput post-genomic studies are now routinely and promisingly investigated in biological and biomedical research. The main statistical approach to select genes differentially expressed between two groups is to apply a t-test, which is subject of criticism in the literature. Numerous alternatives have been developed based on different and innovative variance modeling strategies. However, a critical issue is that selecting a different test usually leads to a different gene list. In this context and given the current tendency to apply the t-test, identifying the most efficient approach in practice remains crucial. To provide elements to answer, we conduct a comparison of eight tests representative of variance modeling strategies in gene expression data: Welch''s t-test, ANOVA [1], Wilcoxon''s test, SAM [2], RVM [3], limma [4], VarMixt [5] and SMVar [6]. Our comparison process relies on four steps (gene list analysis, simulations, spike-in data and re-sampling) to formulate comprehensive and robust conclusions about test performance, in terms of statistical power, false-positive rate, execution time and ease of use. Our results raise concerns about the ability of some methods to control the expected number of false positives at a desirable level. Besides, two tests (limma and VarMixt) show significant improvement compared to the t-test, in particular to deal with small sample sizes. In addition limma presents several practical advantages, so we advocate its application to analyze gene expression data. 相似文献
117.
Directed conversion of Alzheimer's disease patient skin fibroblasts into functional neurons 总被引:2,自引:0,他引:2
118.
Shkreta L Michelle L Toutant J Tremblay ML Chabot B 《The Journal of biological chemistry》2011,286(1):331-340
Alternative splicing often produces effectors with opposite functions in apoptosis. Splicing decisions must therefore be tightly connected to stresses, stimuli, and pathways that control cell survival and cell growth. We have shown previously that PKC signaling prevents the production of proapoptotic Bcl-x(S) to favor the accumulation of the larger antiapoptotic Bcl-x(L) splice variant in 293 cells. Here we show that the genotoxic stress induced by oxaliplatin elicits an ATM-, CHK2-, and p53-dependent splicing switch that favors the production of the proapoptotic Bcl-x(S) variant. This DNA damage-induced splicing shift requires the activity of protein-tyrosine phosphatases. Interestingly, the ATM/CHK2/p53/tyrosine phosphatases pathway activated by oxaliplatin regulates Bcl-x splicing through the same regulatory sequence element (SB1) that receives signals from the PKC pathway. Convergence of the PKC and DNA damage signaling routes may control the abundance of a key splicing repressor because SB1-mediated repression is lost when protein synthesis is impaired but is rescued by blocking proteasome-mediated protein degradation. The SB1 splicing regulatory module therefore receives antagonistic signals from the PKC and the p53-dependent DNA damage response pathways to control the balance of pro- and antiapoptotic Bcl-x splice variants. 相似文献
119.
Laetitia Poidevin Jean-Guy Berrin Chloé Bennati-Granier Anthony Levasseur Isabelle Herpoël-Gimbert Didier Chevret Pedro M. Coutinho Bernard Henrissat Senta Heiss-Blanquet Eric Record 《Applied microbiology and biotechnology》2014,98(17):7457-7469
The genome of the coprophilous fungus Podospora anserina harbors a large and highly diverse set of putative lignocellulose-acting enzymes. In this study, we investigated the enzymatic diversity of a broad range of P. anserina secretomes induced by various carbon sources (dextrin, glucose, xylose, arabinose, lactose, cellobiose, saccharose, Avicel, Solka-floc, birchwood xylan, wheat straw, maize bran, and sugar beet pulp (SBP)). Compared with the Trichoderma reesei enzymatic cocktail, P. anserina secretomes displayed similar cellulase, xylanase, and pectinase activities and greater arabinofuranosidase, arabinanase, and galactanase activities. The secretomes were further tested for their capacity to supplement a T. reesei cocktail. Four of them improved significantly the saccharification yield of steam-exploded wheat straw up to 48 %. Fine analysis of the P. anserina secretomes produced with Avicel and SBP using proteomics revealed a large array of CAZymes with a high number of GH6 and GH7 cellulases, CE1 esterases, GH43 arabinofuranosidases, and AA1 laccase-like multicopper oxidases. Moreover, a preponderance of AA9 (formerly GH61) was exclusively produced in the SBP condition. This study brings additional insights into the P. anserina enzymatic machinery and will facilitate the selection of promising targets for the development of future biorefineries. 相似文献
120.
De novo 2q36.1q36.3 interstitial deletion involving the PAX3 and EPHA4 genes in a fetus with spina bifida and cleft palate 下载免费PDF全文