全文获取类型
收费全文 | 3724篇 |
免费 | 175篇 |
国内免费 | 27篇 |
出版年
2024年 | 9篇 |
2023年 | 75篇 |
2022年 | 174篇 |
2021年 | 314篇 |
2020年 | 158篇 |
2019年 | 183篇 |
2018年 | 249篇 |
2017年 | 152篇 |
2016年 | 223篇 |
2015年 | 269篇 |
2014年 | 293篇 |
2013年 | 287篇 |
2012年 | 301篇 |
2011年 | 252篇 |
2010年 | 159篇 |
2009年 | 141篇 |
2008年 | 139篇 |
2007年 | 124篇 |
2006年 | 86篇 |
2005年 | 79篇 |
2004年 | 52篇 |
2003年 | 42篇 |
2002年 | 33篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 8篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1974年 | 3篇 |
1968年 | 1篇 |
排序方式: 共有3926条查询结果,搜索用时 328 毫秒
951.
Christopher McGuigan Karolina Madela Mohamed Aljarah Arnaud Gilles Andrea Brancale Nicola Zonta Stanley Chamberlain John Vernachio Jeff Hutchins Andrea Hall Brenda Ames Elena Gorovits Babita Ganguly Alexander Kolykhalov Jin Wang Jerry Muhammad Joseph M. Patti Geoffrey Henson 《Bioorganic & medicinal chemistry letters》2010,20(16):4850-4854
We herein report a novel double pro-drug approach applied to the anti-HCV agent 2′-β-C-methyl guanosine. A phosphoramidate ProTide motif and a 6-O-methoxy base pro-drug moiety are combined to generate lipophilic prodrugs of the monophosphate of the guanine nucleoside. Modification of the ester and amino acid moieties lead to a compound INX-08189 that exhibits 10 nM potency in the HCV genotype 1b subgenomic replicon, thus being 500 times more potent than the parent nucleoside. The potency of the lead compound INX-08189 was shown to be consistent with intracellular 2′-C-methyl guanosine triphosphate levels in primary human hepatocytes. The separated diastereomers of INX-08189 were shown to have similar activity in the replicon assay and were also shown to be similar substrates for enzyme processing. INX-08189 has completed investigational new drug enabling studies and has been progressed into human clinical trials for the treatment of chronic HCV infection. 相似文献
952.
Andy W Pang Jeffrey R MacDonald Dalila Pinto John Wei Muhammad A Rafiq Donald F Conrad Hansoo Park Matthew E Hurles Charles Lee J Craig Venter Ewen F Kirkness Samuel Levy Lars Feuk Stephen W Scherer 《Genome biology》2010,11(5):R52
Background
Several genomes have now been sequenced, with millions of genetic variants annotated. While significant progress has been made in mapping single nucleotide polymorphisms (SNPs) and small (<10 bp) insertion/deletions (indels), the annotation of larger structural variants has been less comprehensive. It is still unclear to what extent a typical genome differs from the reference assembly, and the analysis of the genomes sequenced to date have shown varying results for copy number variation (CNV) and inversions.Results
We have combined computational re-analysis of existing whole genome sequence data with novel microarray-based analysis, and detect 12,178 structural variants covering 40.6 Mb that were not reported in the initial sequencing of the first published personal genome. We estimate a total non-SNP variation content of 48.8 Mb in a single genome. Our results indicate that this genome differs from the consensus reference sequence by approximately 1.2% when considering indels/CNVs, 0.1% by SNPs and approximately 0.3% by inversions. The structural variants impact 4,867 genes, and >24% of structural variants would not be imputed by SNP-association.Conclusions
Our results indicate that a large number of structural variants have been unreported in the individual genomes published to date. This significant extent and complexity of structural variants, as well as the growing recognition of their medical relevance, necessitate they be actively studied in health-related analyses of personal genomes. The new catalogue of structural variants generated for this genome provides a crucial resource for future comparison studies. 相似文献953.
Muhammad Fahim Ligia Ayala‐Navarrete Anthony A. Millar Philip J. Larkin 《Plant biotechnology journal》2010,8(7):821-834
Wheat streak mosaic virus (WSMV), vectored by Wheat curl mite, has been of great economic importance in the Great Plains of the United States and Canada. Recently, the virus has been identified in Australia, where it has spread quickly to all major wheat growing areas. The difficulties in finding adequate natural resistance in wheat prompted us to develop transgenic resistance based on RNA interference (RNAi). An RNAi construct was designed to target the nuclear inclusion protein ‘a’ (NIa) gene of WSMV. Wheat was stably cotransformed with two plasmids: pStargate‐NIa expressing hairpin RNA (hpRNA) including WSMV sequence and pCMneoSTLS2 with the nptII selectable marker. When T1 progeny were assayed against WSMV, ten of sixteen families showed complete resistance in transgenic segregants. The resistance was classified as immunity by four criteria: no disease symptoms were produced; ELISA readings were as in uninoculated plants; viral sequences could not be detected by RT‐PCR from leaf extracts; and leaf extracts failed to give infections in susceptible plants when used in test‐inoculation experiments. Southern blot hybridization analysis indicated hpRNA transgene integrated into the wheat genome. Moreover, accumulation of small RNAs derived from the hpRNA transgene sequence positively correlated with immunity. We also showed that the selectable marker gene nptII segregated independently of the hpRNA transgene in some transgenics, and therefore demonstrated that it is possible using these techniques, to produce marker‐free WSMV immune transgenic plants. This is the first report of immunity in wheat to WSMV using a spliceable intron hpRNA strategy. 相似文献
954.
Van Ngoc Thinh Alan R Mootnick Thomas Geissmann Ming Li Thomas Ziegler Muhammad Agil Pierre Moisson Tilo Nadler Lutz Walter Christian Roos 《BMC evolutionary biology》2010,10(1):74
Background
Gibbons or small apes inhabit tropical and subtropical rain forests in Southeast Asia and adjacent regions, and are, next to great apes, our closest living relatives. With up to 16 species, gibbons form the most diverse group of living hominoids, but the number of taxa, their phylogenetic relationships and their phylogeography is controversial. To further the discussion of these issues we analyzed the complete mitochondrial cytochrome b gene from 85 individuals representing all gibbon species, including most subspecies. 相似文献955.
Xiulin Han Angella Dorsey-Oresto Muhammad Malik Jian-Ying Wang Karl Drlica Xilin Zhao Tao Lu 《BMC microbiology》2010,10(1):35
Background
The continuing emergence of antimicrobial resistance requires the development of new compounds and/or enhancers of existing compounds. Genes that protect against the lethal effects of antibiotic stress are potential targets of enhancers. To distinguish such genes from those involved in drug uptake and efflux, a new susceptibility screen is required. 相似文献956.
Muhammad Dain Yazid Shahrul Hisham Zainal Ariffin Sahidan Senafi Mohamad Abdul Razak Rohaya Megat Abdul Wahab 《Cancer cell international》2010,10(1):42
Background
The main morphological features of primitive cells, such as stem and progenitor cells, are that these cells consists only one nucleus. The main purpose of this study was to determine the differentiation capacities of stem and progenitor cells. This study was performed using mononucleated cells originated from murine peripheral blood and MC3T3-E1 cells. Three approaches were used to determine their differentiation capacities: 1) Biochemical assays, 2) Gene expression analysis, and 3) Morphological observations. 相似文献957.
Two heterobimetallic coordination complexes [Co(acac)Cu2(bdmap)2Cl3]·C7H8 (1) and [Co(acac)Cu2(bdmap)2Cl3]·3CH2Cl2 (2) [bdmap = 1,3-Bis(dimethylamino)-2-propanol and acac = 2,4-pentanedionate], have been synthesized by simple chemical technique and characterized by their melting points, elemental composition, FT-IR spectroscopy, mass spectrometry and single crystal X-ray analysis. Thermograms of both the precursors indicated their facile decomposition at relatively low temperature of 454 °C to give stable residual mixture of Cu and CoO. Both the precursors are utilized for the deposition of Cu-CoO thin films by aerosol-assisted chemical vapor deposition (AACVD) equipment at 450 °C on glass substrates that were subsequently characterized for their morphology and composition of the ceramic material. The scanning electron microscopy of copper-cobalt oxide films grown from both the precursors describe highly compact and smooth morphology with homogenously dispersed spherical particles with excellent adhesion properties to the substrates. The EDX analysis shows homogeneous distribution of metallic elements with Cu:Co ratio close to 2:1. Powder X-ray diffraction analysis of the films shows that they are composed of Cu/CoO composite and are crystalline in nature having particle size in the range of 0.3-0.8 μm. 相似文献
958.
Michael K. Dame Narasimharao Bhagavathula Cohra Mankey Marissa DaSilva Tejaswi Paruchuri Muhammad Nadeem Aslam James Varani 《In vitro cellular & developmental biology. Animal》2010,46(2):114-122
Normal and neoplastic human colon tissue obtained at surgery was used to establish conditions for organ culture. Optimal conditions
included an atmosphere of 5% CO2 and 95% O2; tissue partially submerged with mucosa at the gas interface; and serum-free medium with 1.5 mM Ca2+ and a number of growth supplements. Histological, histochemical, and immunohistochemical features that distinguish normal
and neoplastic tissue were preserved over a 2-d period. With normal tissue, this included the presence of elongated crypts
with small, densely packed cells at the crypt base and mucin-containing goblet cells in the upper portion. Ki67 staining,
for proliferating cells, was confined to the lower third of the crypt, while expression of extracellular calcium-sensing receptor
was seen in the upper third and surface epithelium. E-cadherin and β-catenin were expressed throughout the epithelium and
confined to the cell surface. In tumor tissue, the same disorganized, abnormal glandular structures seen at time zero were
present after 2 d. The majority of cells in these structures were mucin-poor, but occasional goblet cells were seen and mucin
staining was present. Ki67 staining was seen throughout the abnormal epithelium and calcium-sensing receptor expression was
weak and variable. E-cadherin was seen at the cell surface (similar to normal tissue), but in some places, there was diffuse
cytoplasmic staining. Finally, intense cytoplasmic and nuclear β-catenin staining was observed in cultured neoplastic tissue. 相似文献
959.
Muhammad Naeem Anjum William Parker Russell Ruo Muhammad Afzal 《Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)》2010,26(1):38-43
The aim of this study was to use different gamma histogram criteria for the comparison of planned dose with irradiated dose distribution and find that what percent of pixels passing a certain criteria imitate a good quality plan. The dose was calculated for 156 patients by inverse planning optimization using the Corvus treatment planning system. Gafchromic films in combination with 2571 0.6 cm3 Farmer type ionization chamber and Farmer 2570/1 electrometer from NE Technology were used to measure the delivered dose in solid water phantom. All the measurements were performed on Varian CL21EX linear accelerator (Varian Medical Systems, Palo Alto, CA) fitted with a Millennium 120 leaf collimator. In this study the mean value of the percent of passing pixels within the region of interest under the criterion of 3% DD and 3 mm DTA is 90.2 ± 7.1% for head and neck cases and 92.2 ± 5.8% for non-head and neck cases. If we choose the criteria of 3% DD and 3 mm DTA then 96.3% head and neck plans have the percent of passing pixels ≥ 75% and 95.1% non-head and neck plans have the percent of passing pixels ≥ 80%. It is evident from the results of this study that the criterion of 5% DD and 3 mm DTA with the percent of passing pixels ≥ 90 for non-head and neck cases while the percent of passing pixels ≥ 85 for head and neck cases endorse that a plan is good. The results of this study may be useful for other institutions which use verification software and EBT films for patient specific IMRT QA. 相似文献
960.
A significant proportion of all incidents of nosocomial infections in acute-care hospitals is due to contaminated catheters. Alternative strategies e.g. antibiotics as well as surface modifications have been devised in an attempt to reduce the incidence of catheter-associated urinary tract infections (CAUTI), but most have proven unsuccessful. Therefore, the race to identify such substances which can combat pathogenic bacteria is ongoing in order to improve the quality of health care. Novel technologies such as the potential use of antiseptic or antimicrobial coatings on catheters hold promise for reducing these infections in the fight against antimicrobial resistance. In this study, the bactericidal activity of newly synthesized tungsten-nanoparticles was tested on clinical multiple drug resistant Escherichia coli isolates from UTI patients with indwelling catheters and Staphylococcus aureus reference strain. The results suggest that the particles tested in this study certainly mediate the inhibition of bacterial growth. We believe that the fabrication of W-NPs on catheters could possibly prevent them from being contaminated by pathogens and hence provide continuous protection of the site. This study is the first of its type testing the antibacterial effects of W-NPs on clinical bacterial isolate from catheterized human UTI case. 相似文献