全文获取类型
收费全文 | 2418篇 |
免费 | 254篇 |
国内免费 | 2篇 |
出版年
2022年 | 14篇 |
2021年 | 28篇 |
2020年 | 16篇 |
2019年 | 16篇 |
2018年 | 15篇 |
2017年 | 21篇 |
2016年 | 63篇 |
2015年 | 113篇 |
2014年 | 113篇 |
2013年 | 144篇 |
2012年 | 172篇 |
2011年 | 183篇 |
2010年 | 98篇 |
2009年 | 106篇 |
2008年 | 147篇 |
2007年 | 172篇 |
2006年 | 155篇 |
2005年 | 146篇 |
2004年 | 147篇 |
2003年 | 146篇 |
2002年 | 124篇 |
2001年 | 18篇 |
2000年 | 19篇 |
1999年 | 35篇 |
1998年 | 39篇 |
1997年 | 30篇 |
1996年 | 29篇 |
1995年 | 21篇 |
1994年 | 21篇 |
1993年 | 16篇 |
1992年 | 14篇 |
1991年 | 19篇 |
1990年 | 23篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 18篇 |
1986年 | 14篇 |
1985年 | 15篇 |
1984年 | 13篇 |
1983年 | 14篇 |
1982年 | 23篇 |
1981年 | 21篇 |
1980年 | 17篇 |
1979年 | 9篇 |
1976年 | 7篇 |
1974年 | 11篇 |
1973年 | 9篇 |
1972年 | 10篇 |
1971年 | 11篇 |
1969年 | 5篇 |
排序方式: 共有2674条查询结果,搜索用时 15 毫秒
231.
Scott T Bates Donna Berg-Lyons J Gregory Caporaso William A Walters Rob Knight Noah Fierer 《The ISME journal》2011,5(5):908-917
Archaea, primarily Crenarchaeota, are common in soil; however, the structure of soil archaeal communities and the factors regulating their diversity and abundance remain poorly understood. Here, we used barcoded pyrosequencing to comprehensively survey archaeal and bacterial communities in 146 soils, representing a multitude of soil and ecosystem types from across the globe. Relative archaeal abundance, the percentage of all 16S rRNA gene sequences recovered that were archaeal, averaged 2% across all soils and ranged from 0% to >10% in individual soils. Soil C:N ratio was the only factor consistently correlated with archaeal relative abundances, being higher in soils with lower C:N ratios. Soil archaea communities were dominated by just two phylotypes from a constrained clade within the Crenarchaeota, which together accounted for >70% of all archaeal sequences obtained in the survey. As one of these phylotypes was closely related to a previously identified putative ammonia oxidizer, we sampled from two long-term nitrogen (N) addition experiments to determine if this taxon responds to experimental manipulations of N availability. Contrary to expectations, the abundance of this dominant taxon, as well as archaea overall, tended to decline with increasing N. This trend was coupled with a concurrent increase in known N-oxidizing bacteria, suggesting competitive interactions between these groups. 相似文献
232.
Camhi SM Bray GA Bouchard C Greenway FL Johnson WD Newton RL Ravussin E Ryan DH Smith SR Katzmarzyk PT 《Obesity (Silver Spring, Md.)》2011,19(2):402-408
The purpose of this study was to examine sex and race differences in the relationship between anthropometric measurements and adiposity in white and African-American (AA) adults. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured with computed tomography (CT). Fat mass (FM) was measured with dual-energy-X-ray absorptiometry (DXA). Correlation coefficients were used to assess the relationship of waist circumference (WC) and BMI to VAT, SAT, and FM within sex-by-race groups. General linear models were used to compare relationships between WC or BMI, and adiposity across sex and race, within age groups (18-39 and 40-64 years). The sample included 1,667 adults (men: 489 white; 120 AA; women: 666 white, 392 AA). WC and BMI correlations were highest for FM and SAT compared to VAT. Women had higher FM levels than men regardless of WC, but the sex difference in FM was attenuated in younger AA adults with a high BMI. For a given level of WC or BMI, women had higher levels of SAT than men; however, significant interactions indicated that the relationship was not consistent across all levels of BMI and WC. Sex and race differences in VAT varied significantly with WC and BMI. In general, white adults had higher levels of VAT than AA adults at higher levels of BMI and WC. Sex differences, and in some instances race differences, in the relationships between anthropometry and fat-specific depots demonstrate that these characteristics need to be considered when predicting adiposity from WC or BMI. 相似文献
233.
Botelho FM Bauer CM Finch D Nikota JK Zavitz CC Kelly A Lambert KN Piper S Foster ML Goldring JJ Wedzicha JA Bassett J Bramson J Iwakura Y Sleeman M Kolbeck R Coyle AJ Humbles AA Stämpfli MR 《PloS one》2011,6(12):e28457
Background
Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide. Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.Methodology and Principal Findings
The objective of this study was to assess IL-1 α and β expression in COPD patients and to investigate their respective roles in perpetuating cigarette smoke-induced inflammation. Functional studies were pursued in smoke-exposed mice using gene-deficient animals, as well as blocking antibodies for IL-1α and β. Here, we demonstrate an underappreciated role for IL-1α expression in COPD. While a strong correlation existed between IL-1α and β levels in patients during stable disease and periods of exacerbation, neutrophilic inflammation was shown to be IL-1α-dependent, and IL-1β- and caspase-1-independent in a murine model of cigarette smoke exposure. As IL-1α was predominantly expressed by hematopoietic cells in COPD patients and in mice exposed to cigarette smoke, studies pursued in bone marrow chimeric mice demonstrated that the crosstalk between IL-1α+ hematopoietic cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation. IL-1α/IL-1R1-dependent activation of the airway epithelium also led to exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed mice, a previously reported model of COPD exacerbation.Conclusions and Significance
This study provides compelling evidence that IL-1α is central to the initiation of smoke-induced neutrophilic inflammation and suggests that IL-1α/IL-1R1 targeted therapies may be relevant for limiting inflammation and exacerbations in COPD. 相似文献234.
235.
236.
Ten replicates of three Mycoplasma hominis strains were tested by microbroth and agar dilution against levofloxacin, moxifloxacin, gatifloxacin, erythromycin, tetracycline, and clindamycin. Both methods provide reproducible results. Agar dilution tends to yield higher MIC values for some drugs. 相似文献
237.
Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte 总被引:23,自引:0,他引:23
Gardai SJ McPhillips KA Frasch SC Janssen WJ Starefeldt A Murphy-Ullrich JE Bratton DL Oldenborg PA Michalak M Henson PM 《Cell》2005,123(2):321-334
Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where "don't eat me" signals are rendered inactive and "eat me" signals, including calreticulin and phosphatidylserine, congregate together and signal for removal. 相似文献
238.
Biomarker discovery in biological fluids 总被引:2,自引:0,他引:2
Gao J Garulacan LA Storm SM Opiteck GJ Dubaquie Y Hefta SA Dambach DM Dongre AR 《Methods (San Diego, Calif.)》2005,35(3):291-302
Discovery of novel protein biomarkers is essential for successful drug discovery and development. These novel protein biomarkers may aid accelerated drug efficacy, response, or toxicity decision making based on their enhanced sensitivity and/or specificity. These biomarkers, if necessary, could eventually be converted into novel diagnostic marker assays. Proteomic platforms developed over the past few years have given us the ability to rapidly identify novel protein biomarkers in various biological matrices from cell cultures (lysates, supernatants) to human clinical samples (serum, plasma, and urine). In this article, we delineate an approach to biomarker discovery. This approach is divided into three steps, (i) identification of markers, (ii) prioritization of identified markers, and (iii) preliminary validation (qualification) of prioritized markers. Using drug-induced idiosyncratic hepatotoxicity as a case study, the article elaborates methods and techniques utilized during the three steps of biomarker discovery process. The first step involves identification of markers using multi-dimensional protein identification technology. The second step involves prioritization of a subset of marker candidates based on several criteria such as availability of reagent set for assay development and literature association to disease biology. The last step of biomarker discovery involves development of preliminary assays to confirm the bio-analytical measurements from the first step, as well as qualify the marker(s) in pre-clinical models, to initiate future marker validation and development. 相似文献
239.
Coros CJ Landthaler M Piazza CL Beauregard A Esposito D Perutka J Lambowitz AM Belfort M 《Molecular microbiology》2005,56(2):509-524
Group II introns are mobile retroelements that invade their cognate intron-minus gene in a process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. Previous studies of the Lactococcus lactis intron Ll.LtrB indicated that in its native host, as in Escherichia coli, retrohoming occurs by the intron RNA reverse splicing into double-stranded DNA (dsDNA) through an endonuclease-dependent pathway. However, in retrotransposition in L. lactis, the intron inserts predominantly into single-stranded DNA (ssDNA), in an endonuclease-independent manner. This work describes the retrotransposition of the Ll.LtrB intron in E. coli, using a retrotransposition indicator gene previously employed in our L. lactis studies. Unlike in L. lactis, in E. coli, Ll.LtrB retrotransposed frequently into dsDNA, and the process was dependent on the endonuclease activity of the intron-encoded protein. Further, the endonuclease-dependent insertions preferentially occurred around the origin and terminus of chromosomal DNA replication. Insertions in E. coli can also occur through an endonuclease-independent pathway, and, as in L. lactis, such events have a more random integration pattern. Together these findings show that Ll.LtrB can retrotranspose through at least two distinct mechanisms and that the host environment influences the choice of integration pathway. Additionally, growth conditions affect the insertion pattern. We propose a model in which DNA replication, compactness of the nucleoid and chromosomal localization influence target site preference. 相似文献
240.
Chesworth R Wessel MD Heyden L Mangano FM Zawistoski M Gegnas L Galluzzo D Lefker B Cameron KO Tickner J Lu B Castleberry TA Petersen DN Brault A Perry P Ng O Owen TA Pan L Ke HZ Brown TA Thompson DD DaSilva-Jardine P 《Bioorganic & medicinal chemistry letters》2005,15(24):5562-5566
A series of ligands with varying heterocyclic cores and substituents that display a range of selectivity’s (up to >100x) for ER-β over ER- are reported. 相似文献