全文获取类型
收费全文 | 1223篇 |
免费 | 93篇 |
出版年
2023年 | 6篇 |
2022年 | 22篇 |
2021年 | 37篇 |
2020年 | 18篇 |
2019年 | 26篇 |
2018年 | 21篇 |
2017年 | 19篇 |
2016年 | 43篇 |
2015年 | 61篇 |
2014年 | 79篇 |
2013年 | 74篇 |
2012年 | 83篇 |
2011年 | 106篇 |
2010年 | 58篇 |
2009年 | 46篇 |
2008年 | 61篇 |
2007年 | 42篇 |
2006年 | 36篇 |
2005年 | 38篇 |
2004年 | 33篇 |
2003年 | 28篇 |
2002年 | 20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 | 17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1316条查询结果,搜索用时 708 毫秒
91.
In enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104 the complex antibiotic resistance gene loci (CRL) found in the region of divergence 1 (RD1) within E. coli genomic island 3 (GI3) contains blaTEM-1, strAB, sul2, tet(A)A, and dfrA7 genes encoding resistance to ampicillin, streptomycin, sulfamethoxazole, tetracycline and trimethoprim respectively. The precise arrangement of antibiotic resistance genes and the role of mobile elements that drove the evolutionary events and created the CRL have not been investigated. We used a combination of bioinformatics and iterative BLASTn searches to determine the micro-evolutionary events that likely led to the formation of the CRL in GI3 using the closed genome sequences of EAHEC O104:H4 strains 2011C-3493 and 2009EL-2050 and high quality draft genomes of EAHEC E. coli O104:H4 isolates from sporadic cases not associated with the initial outbreak. Our analyses indicate that the CRL in GI3 evolved from a progenitor structure that contained an In2-derived class 1 integron in a Tn21/Tn1721 hybrid backbone. Within the hybrid backbone, a Tn6029-family transposon, identified here as Tn6029C abuts the sul1 gene in the 3´-Conserved Segment (-CS) of a class 1 integron generating a unique molecular signature that has only previously been observed in pASL01a, a small plasmid found in commensal E. coli in West Africa. From this common progenitor, independent IS26-mediated events created two novel transposons identified here as Tn6029D and Tn6222 in 2011C-3493 and 2009EL-2050 respectively. Analysis of RD1 within GI3 reveals IS26 has played a crucial role in the assembly of regions within the CRL. 相似文献
92.
Ranju Chowdhury Paulo J.C. Favas J. Pratas M. P. Jonathan P. Sankar Ganesh Santosh Kumar Sarkar 《International journal of phytoremediation》2015,17(9):885-894
The work investigates on the potential of ten mangrove species for absorption, accumulation and partitioning of trace metal(loid)s in individual plant tissues (leaves, bark and root/pneumatophore) at two study sites of Indian Sundarban Wetland. The metal(loid) concentration in host sediments and their geochemical characteristics were also considered. Mangrove sediments showed unique potential in many- fold increase for most metal(loid)s than plant tissues due to their inherent physicochemical properties. The ranges of concentration of trace metal(loid)s for As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn in plant tissue were 0.006–0.31, 0.02–2.97, 0.10–4.80, 0.13–6.49, 4.46–48.30, 9.2–938.1, 0.02–0.13, 9.8–1726, 11–5.41, 0.04–7.64, 3.81–52.20 μg g ?1respectively. The bio- concentration factor (BCF) showed its maximum value (15.5) in Excoecaria agallocha for Cd, suggesting that it can be considered as a high-efficient plant for heavy metal bioaccumulation. Among all metals, Cd and Zn were highly bioaccumulated in E. agallocha (2.97 and 52.2 μg g ?1 respectively. Our findings suggest that the species may be classified as efficient metal trap for Cd in aerial parts, as indicated by higher metal accumulation in the leaves combined with BCF and translocation factor (TF) values. 相似文献
93.
94.
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
95.
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
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
96.
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97.
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
98.
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
99.
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
100.
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