全文获取类型
收费全文 | 787篇 |
免费 | 49篇 |
国内免费 | 4篇 |
专业分类
840篇 |
出版年
2022年 | 7篇 |
2021年 | 6篇 |
2020年 | 10篇 |
2019年 | 6篇 |
2018年 | 19篇 |
2017年 | 18篇 |
2016年 | 22篇 |
2015年 | 23篇 |
2014年 | 38篇 |
2013年 | 40篇 |
2012年 | 42篇 |
2011年 | 27篇 |
2010年 | 28篇 |
2009年 | 19篇 |
2008年 | 27篇 |
2007年 | 33篇 |
2006年 | 23篇 |
2005年 | 25篇 |
2004年 | 30篇 |
2003年 | 16篇 |
2002年 | 28篇 |
2001年 | 22篇 |
2000年 | 20篇 |
1999年 | 16篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 12篇 |
1995年 | 12篇 |
1994年 | 17篇 |
1993年 | 15篇 |
1992年 | 20篇 |
1991年 | 11篇 |
1990年 | 10篇 |
1989年 | 11篇 |
1988年 | 15篇 |
1987年 | 12篇 |
1986年 | 13篇 |
1985年 | 14篇 |
1984年 | 12篇 |
1983年 | 6篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 4篇 |
1978年 | 10篇 |
1977年 | 8篇 |
1973年 | 3篇 |
1969年 | 4篇 |
1950年 | 5篇 |
1928年 | 4篇 |
1876年 | 2篇 |
排序方式: 共有840条查询结果,搜索用时 15 毫秒
31.
Angus R. Hibbins Yahya E. Choonara Pradeep Kumar Lisa C. du Toit Viness Pillay 《AAPS PharmSciTech》2013,14(3):935-949
The purpose of this study was to develop a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity which could be utilized within a binary drug delivery system. Avicel® RC/CL type R-591 was included within the in situ hot melt dispersion mini-pellet formulations to determine the physicomechanical effect this compound would have on the mini-pellet formulations. The physicomechanical properties of the hot melt in situ mini-pellet formulations were mathematically fitting to regression curves. Physicomechanical adjustment of the in situ hot melt dispersion mini-pellet formulations could be mathematically predicted with the derived regression curve equations. The addition of Avicel® RC/CL type R-591 increased the physicomechanical properties such as matrix hardness and increased total disintegration of the in situ hot melt dispersion mini-pellet formulations. The utilization of a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity within a binary drug delivery system would to achieve a synergistically enhance the activity of a drug-carrying entity or a permeation enhancing entity within a single drug delivery unit. The experimental results indicated that weights of the pellets that achieved optimal hardness ranged between 35 and 45 mg. The melt–dispersion formulations disintegrated within shorter time periods and maintained higher ethylenediaminetetraacetic acid (EDTA) concentrations whereas melt–dispersion formulations which included Avicel® had superior physicomechanical properties. Disintegration times ranged between 1,000 s for melt–dispersions containing EDTA and methyloxy polyethylene glycol 2000 (mPEG) only, to >6,000 s for melt–dispersions comprising EDTA, mPEG, and Avicel®. 相似文献
32.
33.
Jane E. Greig Philipp A. du Cros Clair Mills Wilfred Ugwoeruchukwu Andrew Etsetowaghan Adetola Grillo Adetoro Tayo-Adetoro Kunle Omiyale Tim Spelman Daniel P. O’Brien 《PloS one》2013,8(8)
Objectives
In Lagos, Nigeria, Médecins Sans Frontières (MSF) and the Ministry of Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based clinic. We performed a cross-sectional study to compare factors associated with raised viral load between patients with (“experienced”) and without (“naïve”) prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also examined factors influencing ARV adherence in experienced patients prior to clinic entry.Methods
We included adult patients receiving ART from MSF who answered a questionnaire about previous antiretroviral use. Multivariate logistic regression was used to estimate odds ratios (OR) for raised viral load (≥1000 copies/mL).Results
1246 (96%) patients answered: 1075 (86%) reported no, and 171 (14%) some, prior ARV exposure. ARV-naïve patients were more immunosuppressed at baseline: 65% vs 37% (p<0.001) had CD4<200; 17% vs 9% (p = 0.013) were WHO stage 4. Proportionately more experienced than naïve patients had raised viral loads (20% vs 9%, p<0.001) on ART in the MSF/MoH clinic. Raised viral load was associated with prior ARV experience (adjusted OR = 3.74, 95%CI 2.09–6.70, p<0.001) and complete interruption of current ART (adjusted OR = 3.71, 95%CI 2.06–6.68, p<0.001). Higher CD4 at time of VL and a higher self-rated score of recent adherence were associated with lower OR of a raised viral load. Among experienced patients who missed pills before joining MSF/MoH, most common reasons were because ARVS were not affordable (58%) or available (33%), with raised viral load associated with being unsure how to take them (OR = 3.16, 95%CI 1.10–9.12, p = 0.033).Conclusions
Patients previously exposed to ARVs had increased OR of raised viral load. The cost and availability of ARVs were common reasons for missing ARVs before joining the MSF/MoH clinic, and inadequate patient knowledge was associated with raised viral load. 相似文献34.
Chytridiomycosis has been identified as a major cause of global amphibian declines. Despite widespread evidence of Batrachochytrium dendrobatidis infection in South African frogs, sampling for this disease has not focused on threatened species, or whether this pathogen poses a disease risk to these species. This study assessed the occurrence of Bd-infection in South African Red List species. In addition, all known records of infection from South Africa were used to model the ecological niche of Bd to provide a better understanding of spatial patterns and associated disease risk. Presence and prevalence of Bd was determined through quantitative real-time PCR of 360 skin swab samples from 17 threatened species from 38 sites across the country. Average prevalence was 14.8% for threatened species, with pathogen load varying considerably between species. MaxEnt was used to model the predicted distribution of Bd based on 683 positive records for South Africa. The resultant probability threshold map indicated that Bd is largely restricted to the wet eastern and coastal regions of South Africa. A lack of observed adverse impacts on wild threatened populations supports the endemic pathogen hypothesis for southern Africa. However, all threatened species occur within the limits of the predicted distribution for Bd, exposing them to potential Bd-associated risk factors. Predicting pathogen distribution patterns and potential impact is increasingly important for prioritising research and guiding management decisions. 相似文献
35.
Carter D. Wray Marisa W. Friederich Desiree du Sart Sarah Pantaleo Joél Smet Cathlin Kucera Laura Fenton Gunter Scharer Rudy Van Coster Johan L.K. Van Hove 《Mitochondrion》2013,13(6):656-661
New mutations in mitochondrial DNA encoded genes of complex I are rarely reported. An infant developed Leigh disease with infantile spasms. Complex I enzyme activity was deficient and response to increasing coenzyme Q concentrations was reduced. Complex I assembly was intact. A new mutation in MT-ND1 m.3928G>C p.V208L, affecting a conserved amino acid in a critical domain, part of the coenzyme Q binding pocket, was present at high heteroplasmy. The unaffected mother did not carry measurable mutant mitochondrial DNA, but concern remained for gonadal mosaicism. Prenatal testing was possible for a subsequent sibling. The ND1 p.V208L mutation causes Leigh disease. 相似文献
36.
Du Toit Loots Reinart J. Meissner-Roloff Mae Newton-Foot Nicolaas C. Gey van Pittius 《Metabolomics : Official journal of the Metabolomic Society》2013,9(3):631-641
The genome of Mycobacterium, including Mycobacterium tuberculosis, contains five copies of a cluster of genes encoding a novel type VII secretion system, named the ESX gene cluster region. This ESX-3 gene cluster is essential for in vitro growth and is thought to play a role in iron and zinc homeostasis, however, its exact functionality remains an enigma. A metabolomics research approach was subsequently used to compare the metabolite profiles of a M. smegmatis ESX-3 knockout strain to that a wild type parental strain, in order to elucidate its functionality from a metabolic perspective. Statistical analysis of the GC–MS generated data showed a clear separation between the wild type and knockout sample groups, based on the analysed metabolite profiles of these organisms. Of all the metabolite markers identified, various amino acids and metabolite pathways related to these, appeared to be most affected by the ESX-3 knockout, especially those with enzymes regulated by iron and zinc, supporting previous genomics and proteomics generated hypotheses and findings. This study is the first to demonstrate the capacity of using metabolomics, in conjunction with previous genomics and proteomic findings, to identify underlying metabolic changes and confirm previous hypotheses related to the functionality of ESX-3 in Mycobacterium growth and survival. 相似文献
37.
Miles J. Penfold Martin L. Schulman Sarah Clift Lisa du Plessis Peter N. Thompson Marthinus J. Hartman 《Zoo biology》2020,39(5):325-333
The histological effect on the felid uterus of sterilization, via ovariectomy or salpingectomy, is currently unknown. To investigate the association of ovariectomy or salpingectomy with uterine health, it is first necessary to establish if changes are distributed evenly throughout the uterus. Both laparoscopic ovariectomy and salpingectomy with concurrent sampling of the tip of the uterine horn are possible in the cheetah. Currently accepted practice for histopathological screening of the uterus utilizes four biopsy samples. It is not known whether this method accurately reflects the status of the entire uterus. In this study we histologically examined the uteri of six older cheetahs (one 7-year-old and five 10–10.5-year-old animals) via 21 tissue samples (three samples from seven different anatomical regions) per cheetah to determine overall uterine health. Although no defined lesions were detected, mild endometrial gland dilation, assumed to be of no functional consequence, was observed in multiple samples. The odds of observing this dilation was lowest in the uterine body and progressively increased in a cranial direction, being significantly higher at the tip of the uterine horns (OR = 11.5; 95% CI, 2.0-65.1; p = 0.006). This supported the reliability of sampling the tip of the uterine horn to screen for endometrial gland dilation. 相似文献
38.
Estelle Cateau Edouard Randriamalala Antoine Elsendoorn Jean-Philippe Giot Christophe Monegier du Sorbier Marie-Helene Rodier 《Mycopathologia》2013,176(5-6):423-427
Mucorales and Aspergillus are molds responsible for infections in immunocompromised patients. In this report, we describe a case of a rare extensively mixed cutaneous infection caused by Lichtheimia ramosa, Aspergillus fumigatus and Aspergillus terreus in a neutropenic patient suffering from an acute leukemia. The fatal outcome of this patient can be attributed to its hematologic malignancy, the extensive nature of the lesions and the resistance of the strains to antifungals. 相似文献
39.
40.
Ru-Xin Foong Graham Roberts Adam Tobias Fox George du Toit 《Clinical and molecular allergy : CMA》2016,14(1):8