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排序方式: 共有186条查询结果,搜索用时 15 毫秒
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Benoit Visseaux Charlotte Charpentier Gilles Collin Mélanie Bertine Gilles Peytavin Florence Damond Sophie Matheron Eric Lefebvre Fran?oise Brun-Vézinet Diane Descamps ANRS CO HIV- Cohort 《PloS one》2015,10(8)
Background
Maraviroc activity against HIV-2, a virus naturally resistant to different HIV-1 antiretroviral drugs, has been recently demonstrated. The aim of this study was to assess HIV-2 susceptibility to cenicriviroc, a novel, once-daily, dual CCR5 and CCR2 antagonist that has completed Phase 2b development in HIV-1 infection.Methods
Cenicriviroc phenotypic activity has been tested using a PBMC phenotypic susceptibility assay against four R5-, one X4- and one dual-tropic HIV-2 clinical primary isolates. All isolates were obtained by co-cultivation of PHA-activated PBMC from distinct HIV-2-infected CCR5-antagonist-naïve patients included in the French HIV-2 cohort and were previously tested for maraviroc susceptibility using the same protocol. HIV-2 tropism was determined by phenotypic assay using Ghost(3) cell lines.Results
Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc were 0.03, 0.33, 0.45 and 0.98 nM, similar to those observed with maraviroc: 1.13, 0.58, 0.48 and 0.68 nM, respectively. Maximum percentages of inhibition (MPI) of cenicriviroc were 94, 94, 93 and 98%, similar to those observed with maraviroc (93, 90, 82, 100%, respectively). The dual- and X4-tropic HIV-2 strains were resistant to cenicriviroc with EC50 >1000 nM and MPI at 33% and 4%, respectively.Conclusions
In this first study assessing HIV-2 susceptibility to cenicriviroc, we observed an in vitro activity against HIV-2 R5-tropic strains similar to that observed with maraviroc. Thus, cenicriviroc may offer a once-daily treatment opportunity in the limited therapeutic arsenal for HIV-2. Clinical studies are warranted. 相似文献7.
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Eight Danish Holstein cows were milked with a 1-mm thick specially designed soft liner on their right rear teat and a standard
liner mounted under extra high tension on their left rear teat. Four of the animals were overmilked for 5 min. Rear teats
were subjected to ultrasound examination on the first day and to infrared thermography on the second day. Teats were submersed
in ethanol 20 min post-milking on the second day. Ultrasonography measurements showed that teat canal length increased by
30–41% during milking. Twenty minutes after milking, teats milked with modified standard liners still had elongated teat canals
while teats milked with the soft liner were normalized. Overmilking tended to increase teat wall thickness. Approximately
80% of variability in teat canal length, from before teat preparation to after milking, could be explained by changes during
teat preparation. Thermography indicated a general drop in teat temperature during teat preparation. Teat temperature increased
during milking and continued to increase until the ethanol challenge induced a significant drop. Temperatures approached pre-challenge
rather than pre-milking temperatures within 10 minutes after challenge. Teat temperatures were dependent on type of liner.
Mid-teat temperatures post-challenge relative to pre-teat preparation were dependent on overmilking. Thermography and ultrasound
were considered useful methods to indirectly and non invasively evaluate teat tissue integrity. 相似文献
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Hlack Mohammed Jan Arp Frank Chambers Mark Copley Volker Glaab Mark Hammond Derek Solomon Kerry Bradford Theresa Russell Yvonne Sizer Steven C. Nichols Daryl L. Roberts Christopher Shelton Roland Greguletz Jolyon P. Mitchell 《AAPS PharmSciTech》2014,15(5):1126-1137
Compendial methods determining dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distribution (APSD) collect a 4-L air sample containing the aerosol bolus, where the flow, which propagates through the cascade impactor (CI) measurement system from the vacuum source, is used to actuate the inhaler. A previous article described outcomes with two CIs (Andersen eight-stage cascade impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air sample volume was ≤4 L with moderate-resistance DPIs. This article extends that work, examining the hypothesis that DPI flow resistance may be a factor in determining outcomes. APSD measurements were made using the same CI systems with inhalers representing low and high flow resistance extremes (Cyclohaler® and HandiHaler® DPIs, respectively). The ratio of sample volume to internal dead space (normalized volume (V*)) was varied from 0.25 to 1.98 (NGI) and from 0.43 to 3.46 (ACI). Inhaler resistance was a contributing factor to the rate of bolus transfer; the higher resistance DPI completing bolus relocation to the NGI pre-separator via the inlet when V* was as small as 0.25, whereas only ca. 50% of the bolus mass was collected at this condition with the Cyclohaler® DPI. Size fractionation of the bolus from either DPI was completed within the ACI at smaller values of V* than within the NGI. Bolus transfer from the Cyclohaler® capsule and from the HandiHaler® to the ACI system were unaffected by the different flow rise time observed in the two different flow controller systems, and the effects the ACI-based on APSD measurements were marginal. 相似文献
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Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs 总被引:1,自引:0,他引:1
Benz C Copley MR Kent DG Wohrer S Cortes A Aghaeepour N Ma E Mader H Rowe K Day C Treloar D Brinkman RR Eaves CJ 《Cell Stem Cell》2012,10(3):273-283
Adult hematopoietic stem cells (HSCs) with serially transplantable activity comprise two subtypes. One shows a balanced output of mature lymphoid and myeloid cells; the other appears selectively lymphoid deficient. We now show that both of these HSC subtypes are present in the fetal liver (at a 1:10 ratio) with the rarer, lymphoid-deficient HSCs immediately gaining an increased representation in the fetal bone marrow, suggesting that the marrow niche plays a key role in regulating their ensuing preferential amplification. Clonal analysis of HSC expansion posttransplant showed that both subtypes display an extensive but variable self-renewal activity with occasional interconversion. Clonal analysis of their differentiation programs demonstrated functional and molecular as well as quantitative HSC subtype-specific differences in the lymphoid progenitors they generate but an indistinguishable production of multipotent and myeloid-restricted progenitors. These findings establish a level of heterogeneity in HSC differentiation and expansion control that may have relevance to stem cell populations in other hierarchically organized tissues. 相似文献