全文获取类型
收费全文 | 1207篇 |
免费 | 95篇 |
出版年
2023年 | 8篇 |
2022年 | 25篇 |
2021年 | 36篇 |
2020年 | 19篇 |
2019年 | 25篇 |
2018年 | 22篇 |
2017年 | 19篇 |
2016年 | 40篇 |
2015年 | 55篇 |
2014年 | 80篇 |
2013年 | 75篇 |
2012年 | 80篇 |
2011年 | 103篇 |
2010年 | 55篇 |
2009年 | 44篇 |
2008年 | 60篇 |
2007年 | 43篇 |
2006年 | 34篇 |
2005年 | 37篇 |
2004年 | 31篇 |
2003年 | 27篇 |
2002年 | 21篇 |
2001年 | 26篇 |
2000年 | 24篇 |
1999年 | 17篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 12篇 |
1993年 | 8篇 |
1992年 | 17篇 |
1991年 | 16篇 |
1990年 | 21篇 |
1989年 | 18篇 |
1988年 | 13篇 |
1987年 | 14篇 |
1986年 | 12篇 |
1985年 | 19篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1979年 | 10篇 |
1978年 | 9篇 |
1977年 | 5篇 |
1976年 | 9篇 |
1975年 | 6篇 |
1973年 | 11篇 |
1971年 | 6篇 |
1970年 | 6篇 |
1969年 | 8篇 |
1965年 | 5篇 |
排序方式: 共有1302条查询结果,搜索用时 15 毫秒
91.
Bo Chen Allison L. Miller Marlon Rebelatto Yambasu Brewah Daniel C. Rowe Lori Clarke Meggan Czapiga Kim Rosenthal Tomozumi Imamichi Yan Chen Chew-Shun Chang Partha S. Chowdhury Brian Naiman Yue Wang De Yang Alison A. Humbles Ronald Herbst Gary P. Sims 《PloS one》2015,10(2)
Release of endogenous damage associated molecular patterns (DAMPs), including members of the S100 family, are associated with infection, cellular stress, tissue damage and cancer. The extracellular functions of this family of calcium binding proteins, particularly S100A8, S100A9 and S100A12, are being delineated. They appear to mediate their functions via receptor for advanced glycation endproducts (RAGE) or TLR4, but there remains considerable uncertainty over the relative physiological roles of these DAMPs and their pattern recognition receptors. In this study, we surveyed the capacity of S100 proteins to induce proinflammatory cytokines and cell migration, and the contribution RAGE and TLR4 to mediate these responses in vitro. Using adenoviral delivery of murine S100A9, we also examined the potential for S100A9 homodimers to trigger lung inflammation in vivo. S100A8, S100A9 and S100A12, but not the S100A8/A9 heterodimer, induced modest levels of TLR4-mediated cytokine production from human PBMC. In contrast, for most S100s including S100A9, RAGE blockade inhibited S100-mediated cell migration of THP1 cells and major leukocyte populations, whereas TLR4-blockade had no effect. Intranasal administration of murine S100A9 adenovirus induced a specific, time-dependent predominately macrophage infiltration that coincided with elevated S100A9 levels and proinflammatory cytokines in the BAL fluid. Inflammatory cytokines were markedly ablated in the TLR4-defective mice, but unexpectedly the loss of TLR4 signaling or RAGE-deficiency did not appreciably impact the S100A9-mediated lung pathology or the inflammatory cell infiltrate in the alveolar space. These data demonstrate that physiological levels of S100A9 homodimers can trigger an inflammatory response in vivo, and despite the capacity of RAGE and TLR4 blockade to inhibit responses in vitro, the response is predominately independent of both these receptors. 相似文献
92.
A kinetic study on the Novozyme 435‐catalyzed esterification of free fatty acids with octanol to produce octyl esters
下载免费PDF全文
![点击此处可从《Biotechnology progress》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Octyl esters can serve as an important class of biolubricant components replacing their mineral oil counterparts. The purpose of the current work was to investigate the enzymatic esterification reaction of free fatty acids (FFA, from waste cooking oil) with octanol in a solvent‐free system using a commercial lipase Novozyme 435. It was found that the esterificaton reaction followed the Ping‐pong bi‐bi kinetics with no inhibition by substrates or products within the studied concentration range. The maximum reaction rate was estimated to be 0.041 mol L?1 g?1 h?1. Additionally, the stability of Novozyme 435 in the current reaction system was studied by determining its activity and final conversion of FFA to esters after 12 successive utilizations. Novozyme 435 exhibited almost 100% enzyme activity up to 7 cycles of reaction and gradually decreased (by 5%) thereafter. The kinetic parameters evaluated from the study shall assist in the design of reactors for large‐scale production of octyl esters from a cheap biomass source. The enzyme reusability data can further facilitate mass production by curtailing the cost of expensive enzyme consumption. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1494–1499, 2015 相似文献
93.
Mahfuzar Rahman Fatema Tuz Jhohura Sabuj Kanti Mistry Tridib Roy Chowdhury Tanveen Ishaque Rasheduzzaman Shah Kaosar Afsana 《PloS one》2015,10(9)
Objectives
A community based approach before, during and after child birth has been proven effective address the burden of maternal, neonatal and child morbidity and mortality in the low and middle income countries. We aimed to examine the overall change in maternal and newborn health outcomes due the “Improved Maternal Newborn and Child Survival” (IMNCS) project, which was implemented by BRAC in rural communities of Bangladesh.Methods
The intervention was implemented in four districts for duration of 5-years, while two districts served as comparison areas. The intervention was delivered by community health workers who were trained on essential maternal, neonatal and child health care services. A baseline survey was conducted in 2008 among 7, 200 women with pregnancy outcome in last year or having a currently alive child of 12–59 months. A follow-up survey was administered in 2012–13 among 4, 800 women of similar characteristics in the same villages.Findings
We observed significant improvements in maternal and essential newborn care in intervention areas over time, especially in health care seeking behaviors. The proportion of births taking place at home declined in the intervention districts from 84.3% at baseline to 71.2% at end line (P<0.001). Proportion of deliveries with skilled attendant was higher in intervention districts (28%) compared to comparison districts (27.4%). The number of deliveries was almost doubled at public sector facility comparing with baseline (P<0.001). Significant improvement was also observed in healthy cord care practice, delayed bathing of the new-born and reduction of infant mortality in intervention districts compared to that of comparison districts.Conclusions
This study demonstrates that community-based efforts offer encouraging evidence and value for combining maternal, neonatal and child health care package. This approach might be considered at larger scale in similar settings with limited resources. 相似文献94.
Susan R. McGlashan Martin M. Knight Tina T. Chowdhury Purva Joshi Cynthia G. Jensen Sarah Kennedy Charles A. Poole 《Cell biology international》2010,34(5):441-446
The pathways by which chondrocytes of articular cartilage sense their mechanical environment are unclear. Compelling structural evidence suggests that chondrocyte primary cilia are mechanosensory organelles. This study used a 3D agarose culture model to examine the effect of compressive strain on chondrocyte cilia. Chondrocyte/agarose constructs were subjected to cyclic compression (0–15%; 1 Hz) for 0.5–48 h. Additional constructs were compressed for 48 h and allowed to recover for 72 h in uncompressed free‐swelling conditions. Incidence and length of cilia labelled with anti‐acetylated α‐tubulin were examined using confocal microscopy. In free‐swelling chondrocytes, these parameters increased progressively, but showed a significant decrease following 24 or 48 h compression. A 72 h recovery partially reversed this effect. The reduced cilia incidence and length were not due to increased cell division. We therefore propose that control of primary cilia length is an adaptive signalling mechanism in response to varying levels and duration of mechanical loads during joint activity. 相似文献
95.
Das B Chowdhury C Kumar D Sen R Roy R Das P Chatterjee M 《Bioorganic & medicinal chemistry letters》2010,20(23):6947-6950
A series of analogues of andrographolide, prepared through chemo-selective functionalization at C14 hydroxy, have been evaluated for in vitro cytotoxicities against human leukemic cell lines. Two of the analogues (6a, 9b) exhibited significant potency. Preliminary studies on structure-activity relationship (SAR) revealed that the α-alkylidene-γ-butyrolactone moiety of andrographolide played a major role in the activity profile. The structures of the analogues were established through spectroscopic and analytical data. 相似文献
96.
Sumesh Eswaran Airody Vasudeva Adhikari Nishith K. Pal Imran H. Chowdhury 《Bioorganic & medicinal chemistry letters》2010,20(3):1040-1044
A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC2), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis. 相似文献
97.
E. Hampton Sessions Michael Smolinski Bo Wang Bozena Frackowiak Sarwat Chowdhury Yan Yin Yen Ting Chen Claudia Ruiz Li Lin Jennifer Pocas Thomas Schröter Michael D. Cameron Philip LoGrasso Yangbo Feng Thomas D. Bannister 《Bioorganic & medicinal chemistry letters》2010,20(6):1939-1943
Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC50 <10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA). 相似文献
98.
Morshed A. Chowdhury Khaled R.A. Abdellatif Ying Dong Gang Yu Zhangjian Huang Moshfiqur Rahman Dipankar Das Carlos A. Velázquez Mavanur R. Suresh Edward E. Knaus 《Bioorganic & medicinal chemistry letters》2010,20(4):1324-1329
A new group of hybrid nitric oxide (NO) releasing anti-inflammatory (AI) coxib prodrugs (NO-coxibs) wherein the para-tolyl moiety present in celecoxib was replaced by a N-(4-nitrooxybutyl)piperidyl 15a–b, or N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridyl 17a–b, NO-donor moiety was synthesized. All compounds released a low amount of NO upon incubation with phosphate buffered saline (PBS) at pH 7.4 (2.4–5.8% range). In comparison, the percentage NO released was higher (3.1–8.4% range) when these nitrate prodrugs were incubated in the presence of l-cysteine. In vitro COX-1/COX-2 isozyme inhibition studies showed this group of compounds are moderately more potent, and hence selective, inhibitors of the COX-2 relative to the COX-1 enzyme. AI structure–activity relationship data acquired showed that compounds having a MeSO2 COX-2 pharmacophore exhibited superior AI activity compared to analogs having a H2NSO2 substituent. Compounds having a MeSO2 COX-2 pharmacophore in conjunction with a N-(4-nitrooxybutyl)piperidyl (ED50 = 132.4 mg/kg po), or a N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridyl (ED50 = 118.4 mg/kg po), moiety exhibited an AI potency profile that is similar to aspirin (ED50 = 128.7 mg/kg po) but lower than ibuprofen (ED50 = 67.4 mg/kg po). 相似文献
99.
We administered recombinant SV40-derived viral vectors (rSV40s) intravenously to mice with or without prior intraperitoneal injection of mannitol to deliver transgenes to the central nervous system (CNS). We detected transgene-expressing cells (mainly neurons) most prominently in the cortex and spinal cord; prior intraperitoneal mannitol injection increased CNS gene delivery tenfold. Intravenous injection of rSV40s, particularly with mannitol pretreatment, resulted in extensive expression of multiple transgenes throughout the CNS. 相似文献
100.