全文获取类型
收费全文 | 78854篇 |
免费 | 6539篇 |
国内免费 | 4888篇 |
专业分类
90281篇 |
出版年
2024年 | 138篇 |
2023年 | 901篇 |
2022年 | 2075篇 |
2021年 | 3602篇 |
2020年 | 2330篇 |
2019年 | 2838篇 |
2018年 | 2869篇 |
2017年 | 2030篇 |
2016年 | 2873篇 |
2015年 | 4586篇 |
2014年 | 5295篇 |
2013年 | 5966篇 |
2012年 | 6900篇 |
2011年 | 6354篇 |
2010年 | 3818篇 |
2009年 | 3373篇 |
2008年 | 4114篇 |
2007年 | 3654篇 |
2006年 | 3171篇 |
2005年 | 2681篇 |
2004年 | 2276篇 |
2003年 | 1972篇 |
2002年 | 1731篇 |
2001年 | 1559篇 |
2000年 | 1565篇 |
1999年 | 1447篇 |
1998年 | 847篇 |
1997年 | 797篇 |
1996年 | 808篇 |
1995年 | 736篇 |
1994年 | 687篇 |
1993年 | 530篇 |
1992年 | 818篇 |
1991年 | 657篇 |
1990年 | 601篇 |
1989年 | 531篇 |
1988年 | 421篇 |
1987年 | 362篇 |
1986年 | 336篇 |
1985年 | 299篇 |
1984年 | 221篇 |
1983年 | 199篇 |
1982年 | 112篇 |
1981年 | 118篇 |
1980年 | 86篇 |
1979年 | 147篇 |
1978年 | 84篇 |
1977年 | 95篇 |
1975年 | 111篇 |
1974年 | 116篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Ling Xie Cui Liu Li Wang Harsha P. Gunawardena Yanbao Yu Ruyun Du Debra J. Taxman Penggao Dai Zhen Yan Jing Yu Stephen P. Holly Leslie V. Parise Yisong Y. Wan Jenny P. Ting Xian Chen 《Cell reports》2013,3(3):678-688
Highlights? PP2Ac is constitutively activated and targets MyD88 in LPS-tolerized macrophages ? Constitutively active PP2Ac shifts a proinflammatory MyD88 to its prosurvival mode ? Constitutively active PP2Ac reprograms gene-specific chromatin modification landscape ? Constitutively active PP2Ac broadly defines ET at both signaling and epigenetic levels 相似文献
992.
Protein sequence contains clues to its function. Functional prediction from sequence presents a challenge particularly for proteins that have low or no sequence similarity to proteins of known function. Recently, machine learning methods have been explored for predicting functional class of proteins from sequence-derived properties independent of sequence similarity, which showed promising potential for low- and non-homologous proteins. These methods can thus be explored as potential tools to complement alignment- and clustering-based methods for predicting protein function. This article reviews the strategies, current progresses, and underlying difficulties in using machine learning methods for predicting the functional class of proteins. The relevant software and web-servers are described. The reported prediction performances in the application of these methods are also presented, which need to be interpreted with caution as they are dependent on such factors as datasets used and choice of parameters. 相似文献
993.
Chun-Long Li Mei Wang Xiao-Meng Wu Dong-Hua Chen Hong-Jun Lv Jian-Lin Shen Zhu Qiao Wei Zhang 《Plant physiology》2016,170(2):1090-1104
994.
Catriona L. Halliday Monica A. Slavin Sharon C.-A. Chen 《Current fungal infection reports》2017,11(3):124-133
Purpose of Review
Resistance to antifungal drugs amongst Candida species is a growing concern, and azole resistance may be emerging in Cryptococcus species. This review provides a contemporary perspective, relevant to the clinical mycology laboratory, of antifungal susceptibility testing of these fungi, focussing on the challenges of phenotypic and genotypic methodologies to detect drug resistance.Recent Findings
Standardised CLSI and EUCAST broth microdilution (BMD) susceptibility testing methods are the benchmark to determine clinical breakpoints (CBPs) and/or epidemiological cut-off values (ECVs) MICs for Candida and Cryptococcus spp. Commercial methods may be used but caution is required when employing BMD CBPs/ECVs to interpret results. Species-specific CBPs/ECVs for Candida spp. generally correlate well with predicting likelihood of therapeutic failure or of presence of a drug resistance mechanism with the exception of the echinocandins where the presence of specific FKS gene mutations and not the MIC correlates most accurately with clinical outcome. The relationship of presence of one or more mechanisms of azole resistance and drug MICs is uncertain. Next generation sequencing technology is offering insights into the relationships between susceptibility results obtained by phenotypic and genotypic methods. For Cryptococcus spp., CBPs are not established but species- and genetic type-specific EVCs are useful for guiding therapy where clinically indicated. Isolates of genotype VGII appear to exhibit the highest MICs.Summary
Antifungal susceptibility testing of yeasts is important to detect drug resistance. For Candida spp., MICs have clinical utility for the azoles but detecting echinocandin resistance by genotypic methods is preferred. For Cryptococcus spp., ECVs are useful in guiding therapy.995.
Xiang Chen Heng Zou Li Xiong Sheng-Fu Huang Xiong-Ying Miao Yu Wen 《World journal of surgical oncology》2017,15(1):216
Background
The purpose of this case series is to investigate the relationship between splenic thickness (ST) and postoperative outcomes after hepatic resection in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients.Methods
The clinical data of 320 patients with HBV-associated HCC who had undergone liver resection were retrospectively analyzed. The value of ST in predicting postoperative outcomes was evaluated.Results
A total of 320 patients were enrolled in the study. An increase in ST was significantly associated with an increase in portal vein diameter (PVD), indocyanine green retention rate 15 min (ICG R15), and total bilirubin (TBIL); however, it was negatively correlated with platelet count (PLT). Post-hepatectomy liver failure (PHLF) occurred in 35 (10.9%) patients. Multivariate logistic regression analysis showed that ST was an independent predictor of morbidity and mortality after hepatectomy. Meanwhile, ST was associated with an almost sixfold increased risk for developing perioperative complications (OR 5.678; 95% CI 2.873 to 11.224; P?<?0.001) and almost 13-fold increased risk for mortality after hepatectomy (OR 13.007; 95% CI 1.238 to 136.627; P?=?0.033).The area under the receiver operating characteristic (ROC) curve (AUC) of ST for predicting the incidence of PHLF was 0.754 (95% confidence interval (CI) 0.667 to 0.841; P?<?0.001), with a sensitivity of 57.1% and a specificity of 82.5%, which were significantly greater than those of the ICG R15 level (AUC 0.670; 95% CI 0.560 to 0.779; P?<?0.001). The critical value of ST was 43.5 mm.Conclusions
ST, which is an easy, inexpensive, and routinely available perioperative marker, showed a favorable predictive value for postoperative outcomes in HBV-associated HCC patients.996.
Nan Liu Hui Chen Bing Wu Ying Li Max Wintermark Alan Jackson Jun Hu Yongwei Zhang Zihua Su Guangming Zhu Weiwei Zhang 《Molecular neurobiology》2017,54(4):2539-2546
In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K trans) as a biomarker for blood–brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K trans (K trans-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K trans-PIV, and smaller FIV (P?<?0.001). K trans-PIV showed good correlation with FIV (P?<?00.001, R 2?=?0.6997). In the regression analyses, K trans-PIV was the best predictor of clinical outcomes (P?=?0.009, odds ratio (OR)?=?1.960) and also the best predictor for FIV (F?=?75.590, P?<?0.0001). In conclusion, combining PCT and K trans maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes. 相似文献
997.
998.
Chen WT Hendrickson RL Huang CP Sherman D Geng T Bhunia AK Ladisch MR 《Biotechnology and bioengineering》2005,89(3):263-273
Detection of the foodborne pathogen Listeria monocytogenes requires that food samples be processed to remove proteins and lipids, concentrate microorganisms to a detectable concentration, and recover the concentrated cells in a small volume compatible with micron-scale biochips. Mechanistic considerations addressed in this research include the roles of membrane structure, pore size, and detergents in maximizing recovery of cells from a complex biological fluid. The fluid in this case was a food sample (hotdog extract) inoculated with L. monocytogenes. This study showed how membrane filtration using a syringe filter is able to concentrate L. monocytogenes by 95x with up to 95% recovery of living microorganisms by concentrating 50 mL of food sample into a volume of 500 microL. Tween 20 was added to the sample to prevent irreversible adsorption of the microorganism to the membrane and thereby help to ensure high recovery. Comparison of polycarbonate, mixed cellulose, nylon, and PVDF membranes with 0.2 to 0.45 microm pores showed the 0.2 microm polycarbonate membrane with straight through, mono-radial pores gives the highest recovery of living microorganisms. The mixed cellulose, nylon, and PVDF membranes have a fibrous structure whose characteristic openings are much larger than their effective pore size cut-offs of 0.22 or 0.45 microm. We define conditions for rapid membrane-based cell concentration and recovery that has the potential to supplant enrichment steps that require a day or more. This approach has the added benefit of facilitating examination of a large amount of fluid volume by reducing its volume to a range that is compatible with the microliter scales of biochip or other biosensor detection systems. 相似文献
999.
A non-stationary model for functional mapping of complex traits 总被引:3,自引:0,他引:3
SUMMARY: Understanding the genetic control of growth is fundamental to agricultural, evolutionary and biomedical genetic research. In this article, we present a statistical model for mapping quantitative trait loci (QTL) that are responsible for genetic differences in growth trajectories during ontogenetic development. This model is derived within the maximum likelihood context, implemented with the expectation-maximization algorithm. We incorporate mathematical aspects of growth processes to model the mean vector and structured antedependence models to approximate time-dependent covariance matrices for longitudinal traits. Our model has been employed to map QTL that affect body mass growth trajectories in both male and female mice of an F2 population derived from the Large and Small mouse strains. The results from this model are compared with those from the autoregressive-based functional mapping approach. Based on results from computer simulation studies, we suggest that these two models are alternative to one another and should be used simultaneously for the same dataset. 相似文献
1000.
Poon B Safrit JT McClure H Kitchen C Hsu JF Gudeman V Petropoulos C Wrin T Chen IS Grovit-Ferbas K 《Journal of virology》2005,79(8):4927-4935
The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development. 相似文献