全文获取类型
收费全文 | 1137篇 |
免费 | 75篇 |
出版年
2023年 | 8篇 |
2022年 | 24篇 |
2021年 | 60篇 |
2020年 | 27篇 |
2019年 | 20篇 |
2018年 | 41篇 |
2017年 | 32篇 |
2016年 | 35篇 |
2015年 | 45篇 |
2014年 | 57篇 |
2013年 | 80篇 |
2012年 | 103篇 |
2011年 | 76篇 |
2010年 | 47篇 |
2009年 | 31篇 |
2008年 | 48篇 |
2007年 | 42篇 |
2006年 | 37篇 |
2005年 | 38篇 |
2004年 | 18篇 |
2003年 | 15篇 |
2002年 | 18篇 |
2001年 | 19篇 |
2000年 | 20篇 |
1999年 | 14篇 |
1995年 | 5篇 |
1993年 | 8篇 |
1992年 | 11篇 |
1991年 | 15篇 |
1990年 | 14篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1980年 | 7篇 |
1979年 | 13篇 |
1978年 | 7篇 |
1977年 | 8篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1974年 | 6篇 |
1973年 | 11篇 |
1972年 | 11篇 |
1971年 | 8篇 |
1970年 | 6篇 |
1966年 | 6篇 |
排序方式: 共有1212条查询结果,搜索用时 406 毫秒
81.
Simon I. Hay Emelda A. Okiro Peter W. Gething Anand P. Patil Andrew J. Tatem Carlos A. Guerra Robert W. Snow 《PLoS medicine》2010,7(6)
Background
The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches.Methods and Findings
In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales.Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349–552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk.Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques.Conclusions and Significance
Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated. Please see later in the article for the Editors'' Summary 相似文献82.
83.
Semi-interpenetrating polymer network (IPN) microspheres of acrylamide grafted on dextran (AAm-g-Dex) and chitosan (CS) were prepared by emulsion-crosslinking method using glutaraldehyde (GA) as a crosslinker. The grafting efficiency was found to be 94%. Acyclovir, an antiviral drug with limited water solubility, was successfully encapsulated into IPN microspheres by varying the ratio of AAm-g-Dex and CS, % drug loading and amount of GA. Microspheres were characterized by FT-IR spectroscopy to assess the formation of IPN structure and to confirm the absence of chemical interactions between drug, polymer and crosslinking agent. Particle size was measured using laser light scattering technique. Microspheres with average particle sizes in the range of 265–388 μm were obtained. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) studies were performed to understand the crystalline nature of drug after encapsulation into IPN microspheres. Acyclovir encapsulation of up to 79.6% was achieved as measured by UV spectroscopy. Both equilibrium and dynamic swelling studies were performed in 0.1 N HCl. Diffusion coefficients (D) and diffusional exponents (n) for water transport were determined using an empirical equation. In vitro release studies indicated the dependence of drug release rates on both the extent of crosslinking and amount of AAm-g-Dex used in preparing microspheres; the slow release was extended up to 12 h. The release rates were fitted to an empirical equation to compute the diffusional exponent (n), which indicated non-Fickian trend for the release of acyclovir. 相似文献
84.
85.
Kaur K Patel SR Patil P Jain M Khan SI Jacob MR Ganesan S Tekwani BL Jain R 《Bioorganic & medicinal chemistry》2007,15(2):915-930
We report the synthesis, in vitro antiprotozoal (against Plasmodium and Leishmania), antimicrobial, cytotoxicity (Vero and MetHb-producing properties), and in vivo antimalarial activities of two series of 8-quinolinamines. N1-{4-[2-(tert-Butyl)-6-methoxy-8-quinolylamino]pentyl}-(2S/2R)-2-aminosubstitutedamides (21-33) and N1-[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-(2S/2R)-2-aminosubstitutedamides (51-63) were synthesized in six steps from 6-methoxy-8-nitroquinoline and 4-methoxy-2-nitro-5-pentyloxyaniline, respectively. Several analogs displayed promising antimalarial activity in vitro against Plasmodium falciparum D6 (chloroquine-sensitive) and W2 (chloroquine-resistant) clones with high selectivity indices versus mammalian cells. The most promising analogs (21-24) also displayed potent antimalarial activity in vivo in a Plasmodium berghei-infected mouse model. Most interestingly, many analogs exhibited promising in vitro antileishmanial activity against Leishmania donovani promastigotes, and antimicrobial activities against a panel of pathogenic bacteria and fungi. Several analogs, notably 21-24, 26-32, and 60, showed less MetHb formation compared to primaquine indicating the potential of these compounds in 8-quinolinamine-based antimalarial drug development. 相似文献
86.
Kusal K. Das Amrita Das Gupta Salim A. Dhundasi Ashok M. Patil Swastika N. Das Jeevan G. Ambekar 《Biometals》2007,20(2):177-184
In this experimental study, we investigated whether l-ascorbic acid has any influence on the blood antioxidant defense system, lipid peroxidation and hematological parameters
of the albino rats exposed to nickel sulfate(NiSO4).Twenty four adult rats were divided into four groups of six animals in each group. The control rats were untreated and comprised
Group I. Group II rats were administered nickel sulfate (2.0 mg/100 g b.wt.; intraperitonially, i.p.). Group II rats were
treated orally l-ascorbic acid (50 mg/100 g b.wt.) and Group IV rats were given both nickel sulfate and l-ascorbic acid simultaneously on alternate days until the tenth dose. The hematological parameters were assessed: red blood
corpuscle counts, packed cell volume %, hemoglobin concentration, white blood corpuscle counts and platelets count decreased
significantly and clotting time increased significantly in nickel treated rats. We also observed increase malondialdehyde
(MDA) and decrease glutathione level (GSH) in erythrocytes of nickel treated rats. The activities of erythrocyte antioxidant
enzymes like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were significantly increased in
rats treated with nickel sulfate. Simultaneously treatment of l-ascorbic acid exhibited a possible protective role on the toxic effect of nickel sulfate on the hematological values, erythrocyte
MDA and GSH concentrations as well as antioxidant enzymatic defense system. 相似文献
87.
Begley U Dyavaiah M Patil A Rooney JP DiRenzo D Young CM Conklin DS Zitomer RS Begley TJ 《Molecular cell》2007,28(5):860-870
88.
We had earlier shown that human foetal epithelial cells (WISH), growth-inhibited by interferon gamma (IFNgamma), were reversibly detained at a point prior to DNA synthesis. In the present study, we determined the window of action of IFNgamma in the G1 phase duration and the exact point of detention of WISH cells in cell cycle progression with respect to the known points of detention by the inhibitors of DNA replication initiation (aphidicolin and carbonyl diphosphonate) and of activation of replication protein A (6-dimethylaminopurine), of which RPA activation being the earlier event compared to DNA replication initiation in cell cycle progression. WISH cells, which were released from IFNgamma-induced arrest, permeabilised and exposed independently to these inhibitors show that IFNgamma detains WISH cells prior to initiation of DNA synthesis. Further, exposure of IFNalpha-synchronized (at G0/G1) or mimosine-synchronized (at G1/S) WISH cells to IFNgamma, which was added at different time points post-release from the synchronizing agent, showed that the cells were promptly responsive to the growth inhibitory action of IFNgamma only during the first 11h in G1 phase. Taken together, these results suggest that IFNgamma inhibits growth of WISH cells by detaining them at a point prior to initiation of DNA synthesis and that the IFN acts within the first 11h in G1 phase of the cell cycle. 相似文献
89.
The cytosolic protein degradation pathway, involving ATP-dependent proteases and ATP-independent peptidases, is important for modulating several cellular responses. The involvement of pathogen-encoded ATP-dependent proteases is well established during infection. However, the roles of ATP-independent peptidases in this process are not well studied. The functional role of Peptidase N (PepN), an ATP-independent enzyme belonging to the M1 family, during systemic infection of mice by Salmonella enterica serovar Typhimurium (Salmonella typhimurium) was investigated. In a systemic model of infection, the number of CFU of S. typhimurium containing a targeted deletion in peptidase N (DeltapepN), compared with wild type, was significantly higher in the lymph node and spleen. In addition, S. typhimurium replicated in the thymus and greatly reduced the number of immature CD4(+)CD8(+) thymocytes in a dose- and time-dependent manner. Strains lacking or overexpressing pepN were used to show that the reduction in the number of thymocytes, but not lymph node cells, depends on a critical number of CFU. These findings establish a role for PepN in reducing the in vivo CFU of S. typhimurium during systemic infection. The implications of these results, in the context of the roles of proteases and peptidases, during host-pathogen interactions are discussed. 相似文献
90.
Red Mexican grapefruit: a novel source for bioactive limonoids and their antioxidant activity 总被引:3,自引:0,他引:3
Mandadi KK Jayaprakasha GK Bhat NG Patil BS 《Zeitschrift für Naturforschung. C, Journal of biosciences》2007,62(3-4):179-188
Citrus limonoids have shown to inhibit the growth of cancer in colon, lung, mouth, stomach and breast in animal and cell culture studies. For the first time in the present study, an attempt has been made to isolate antioxidant fractions and five limonoids from red Mexican grapefruit seeds. Defatted seed powder was successively extracted with hexane, ethyl acetate (EtOAc), acetone, methanol (MeOH) and MeOH/water and the extracts were concentrated under vacuum. Radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and total phenolic content were also measured for comparison with the antioxidant capacity in the phosphomolybdenum method for the above extracts. Acetone and MeOH extracts, respectively, showed the highest (85.7%) and lowest (53.3%) radical scavenging activity, at 500 ppm. The total phenolic contents were found to be highest in the acetone extract (15.94%) followed by the MeOH extract (5.92%), ethyl acetate extract (5.54%) and water extract (5.26%). Antioxidant capacity of the extracts as equivalents to ascorbic acid (micromol/g of the extract) was in the order, EtOAc extract > acetone extract > water extract > methanol extract. Furthermore, the EtOAC and acetone extracts were loaded onto silica gel columns to obtain four limonoid aglycons. MeOH fraction was loaded onto a dowex-50 and sepabeads resin column to obtain a limonoid glucoside. The purity of the isolated five compounds was analyzed by HPLC using a C18 column and UV detection at 210 nm. Finally, the structures of the compounds were identified as obacunone, nomilin, limonin, deacetylnomilin (DAN) and limonin-17-beta-D-glucopyranoside (LG) using 1H and 13C NMR studies. 相似文献