全文获取类型
收费全文 | 2020篇 |
免费 | 240篇 |
专业分类
2260篇 |
出版年
2021年 | 35篇 |
2020年 | 14篇 |
2019年 | 18篇 |
2018年 | 20篇 |
2017年 | 20篇 |
2016年 | 37篇 |
2015年 | 69篇 |
2014年 | 63篇 |
2013年 | 93篇 |
2012年 | 94篇 |
2011年 | 100篇 |
2010年 | 61篇 |
2009年 | 59篇 |
2008年 | 91篇 |
2007年 | 79篇 |
2006年 | 82篇 |
2005年 | 92篇 |
2004年 | 94篇 |
2003年 | 70篇 |
2002年 | 56篇 |
2001年 | 45篇 |
2000年 | 53篇 |
1999年 | 62篇 |
1998年 | 34篇 |
1997年 | 26篇 |
1996年 | 28篇 |
1995年 | 20篇 |
1994年 | 25篇 |
1993年 | 15篇 |
1992年 | 47篇 |
1991年 | 35篇 |
1990年 | 39篇 |
1989年 | 41篇 |
1988年 | 34篇 |
1987年 | 37篇 |
1986年 | 21篇 |
1985年 | 30篇 |
1984年 | 20篇 |
1983年 | 15篇 |
1982年 | 14篇 |
1980年 | 19篇 |
1979年 | 28篇 |
1978年 | 24篇 |
1977年 | 24篇 |
1975年 | 15篇 |
1974年 | 21篇 |
1972年 | 12篇 |
1971年 | 14篇 |
1970年 | 14篇 |
1967年 | 16篇 |
排序方式: 共有2260条查询结果,搜索用时 15 毫秒
991.
?ngelo C. Salvador Inês Baptista António S. Barros Newton C. M. Gomes ?ngela Cunha Adelaide Almeida Silvia M. Rocha 《PloS one》2013,8(4)
A novel approach based on headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC×GC–ToFMS) was developed for the simultaneous screening of microbial and mite contamination level in cereals and coffee beans. The proposed approach emerges as a powerful tool for the rapid assessment of the microbial contamination level (ca. 70 min versus ca. 72 to 120 h for bacteria and fungi, respectively, using conventional plate counts), and mite contamination (ca. 70 min versus ca. 24 h). A full-factorial design was performed for optimization of the SPME experimental parameters. The methodology was applied to three types of rice (rough, brown, and white rice), oat, wheat, and green and roasted coffee beans. Simultaneously, microbiological analysis of the samples (total aerobic microorganisms, moulds, and yeasts) was performed by conventional plate counts. A set of 54 volatile markers was selected among all the compounds detected by GC×GC–ToFMS. Principal Component Analysis (PCA) was applied in order to establish a relationship between potential volatile markers and the level of microbial contamination. Methylbenzene, 3-octanone, 2-nonanone, 2-methyl-3-pentanol, 1-octen-3-ol, and 2-hexanone were associated to samples with higher microbial contamination level, especially in rough rice. Moreover, oat exhibited a high GC peak area of 2-hydroxy-6-methylbenzaldehyde, a sexual and alarm pheromone for adult mites, which in the other matrices appeared as a trace component. The number of mites detected in oat grains was correlated to the GC peak area of the pheromone. The HS-SPME/GC×GC–ToFMS methodology can be regarded as the basis for the development of a rapid and versatile method that can be applied in industry to the simultaneous assessment the level of microbiological contamination and for detection of mites in cereals grains and coffee beans. 相似文献
992.
Denny JC Crawford DC Ritchie MD Bielinski SJ Basford MA Bradford Y Chai HS Bastarache L Zuvich R Peissig P Carrell D Ramirez AH Pathak J Wilke RA Rasmussen L Wang X Pacheco JA Kho AN Hayes MG Weston N Matsumoto M Kopp PA Newton KM Jarvik GP Li R Manolio TA Kullo IJ Chute CG Chisholm RL Larson EB McCarty CA Masys DR Roden DM de Andrade M 《American journal of human genetics》2011,(4):529-542
We repurposed existing genotypes in DNA biobanks across the Electronic Medical Records and Genomics network to perform a genome-wide association study for primary hypothyroidism, the most common thyroid disease. Electronic selection algorithms incorporating billing codes, laboratory values, text queries, and medication records identified 1317 cases and 5053 controls of European ancestry within five electronic medical records (EMRs); the algorithms'' positive predictive values were 92.4% and 98.5% for cases and controls, respectively. Four single-nucleotide polymorphisms (SNPs) in linkage disequilibrium at 9q22 near FOXE1 were associated with hypothyroidism at genome-wide significance, the strongest being rs7850258 (odds ratio [OR] 0.74, p = 3.96 × 10−9). This association was replicated in a set of 263 cases and 1616 controls (OR = 0.60, p = 5.7 × 10−6). A phenome-wide association study (PheWAS) that was performed on this locus with 13,617 individuals and more than 200,000 patient-years of billing data identified associations with additional phenotypes: thyroiditis (OR = 0.58, p = 1.4 × 10−5), nodular (OR = 0.76, p = 3.1 × 10−5) and multinodular (OR = 0.69, p = 3.9 × 10−5) goiters, and thyrotoxicosis (OR = 0.76, p = 1.5 × 10−3), but not Graves disease (OR = 1.03, p = 0.82). Thyroid cancer, previously associated with this locus, was not significantly associated in the PheWAS (OR = 1.29, p = 0.09). The strongest association in the PheWAS was hypothyroidism (OR = 0.76, p = 2.7 × 10−13), which had an odds ratio that was nearly identical to that of the curated case-control population in the primary analysis, providing further validation of the PheWAS method. Our findings indicate that EMR-linked genomic data could allow discovery of genes associated with many diseases without additional genotyping cost. 相似文献
993.
994.
Trujillo JI Huang W Hughes RO Rogier DJ Turner SR Devraj R Morton PA Xue CB Chao G Covington MB Newton RC Metcalf B 《Bioorganic & medicinal chemistry letters》2011,21(6):1827-1831
This report describes the design and synthesis of a series of CCR2 antagonists incorporating novel non-aryl/heteroaryl RHS (right hand side) motifs. Previous SAR in the area has suggested an aryl/heteroaryl substituent as a necessary structural feature for binding to the CCR2 receptor. Herein we describe the SAR with regards to potency (binding to hCCR2), dofetilide activity and metabolic stability (in vitro HLM) for this series. The resulting outcome was the identification of compounds with excellent properties for the investigation of the role of CCR2 in disease. 相似文献
995.
Haggerty TJ Dunn IS Rose LB Newton EE Martin S Riley JL Kurnick JT 《Cancer immunology, immunotherapy : CII》2011,60(1):133-144
While there are many obstacles to immune destruction of autologous tumors, there is mounting evidence that tumor antigen recognition
does occur. Unfortunately, immune recognition rarely controls clinically significant tumors. Even the most effective immune
response will fail if tumors fail to express target antigens. Importantly, reduced tumor antigen expression often results
from changes in gene regulation rather than irrevocable loss of genetic information. Such perturbations are often reversible
by specific compounds or biological mediators, prompting a search for agents with improved antigen-enhancing properties. Some
recent findings have suggested that certain conventional chemotherapeutic agents may have beneficial properties for cancer
treatment beyond their direct cytotoxicities against tumor cells. Accordingly, we screened an important subset of these agents,
topoisomerase inhibitors, for their effects on antigen levels in tumor cells. Our analyses demonstrate upregulation of antigen
expression in a variety of melanoma cell lines and gliomas in response to nanomolar levels of certain specific topoisomerase
inhibitors. To demonstrate the ability of CD8+ T cells to recognize tumors, we assayed cytokine secretion in T cells transfected
with T cell receptors directed against Melan-A/MART-1 antigen. Three days of daunorubicin treatment resulted in enhanced antigen
expression by tumor cells, in turn inducing co-cultured antigen-specific T cells to secrete Interleukin-2 and Interferon-γ.
These results demonstrate that specific topoisomerase inhibitors can augment melanoma antigen production, suggesting that
a combination of chemotherapy and immunotherapy may be of potential value in the treatment of otherwise insensitive cancers. 相似文献
996.
Kinnunen P Sinn I McNaughton BH Newton DW Burns MA Kopelman R 《Biosensors & bioelectronics》2011,26(5):2751-2755
Continuous growth of individual bacteria has been previously studied by direct observation using optical imaging. However, optical microscopy studies are inherently diffraction limited and limited in the number of individual cells that can be continuously monitored. Here we report on the use of the asynchronous magnetic bead rotation (AMBR) sensor, which is not diffraction limited. The AMBR sensor allows for the measurement of nanoscale growth dynamics of individual bacterial cells, over multiple generations. This torque-based magnetic bead sensor monitors variations in drag caused by the attachment and growth of a single bacterial cell. In this manner, we observed the growth and division of individual Escherichia coli, with 80-nm sensitivity to the cell length. Over the life cycle of a cell, we observed up to a 300% increase in the rotational period of the biosensor due to increased cell volume. In addition, we observed single bacterial cell growth response to antibiotics. This work demonstrates the non-microscopy limited AMBR biosensor for monitoring individual cell growth dynamics, including cell elongation, generation time, lag time, and division, as well as their sensitivity to antibiotics. 相似文献
997.
The naphthalene-degrading activity of a Pseudomonas sp. strain isolated from a creosote-contaminated soil was shown to be encoded by the IncP9 plasmid pNF142 by transfer to Pseudomonas putida KT2442. The effects of the inoculant strain KT2442 (pNF142) and of naphthalene contamination on the soil bacterial community were studied in microcosms with the following treatments: (I) soil, (II) soil with naphthalene, (III) soil with naphthalene and inoculated with KT2442 (pNF142). The inoculant became the dominant bacterial population in treatment (III) as evidenced by cultivation and denaturing gradient gel electrophoresis (DGGE) analysis. The bacterial DGGE profiles revealed drastically reduced complexity due to the numerical dominance of the inoculant. However, group-specific fingerprints (beta-proteobacteria, actinobacteria) that excluded KT2442 (pNF142) showed less severe changes in the bacterial community patterns. A major effect of naphthalene on the soil bacterial community was observed in treatment (II) after 21 days. Two dominant bands appeared whose sequences showed the highest similarity to those of Burkholderia sp. RP007 and Nocardia vinaceae based on 16S rRNA gene sequencing. These bands were less intense in treatment (III). The increased abundance of RP007-like populations due to naphthalene contamination was also confirmed by PCR amplification of the phnAc gene. The nahAc and nahH genes were detected in DNA and cDNA only in treatment III. Although the inoculant strain KT2442 (pNF142) showed good survival and expression of genes involved in naphthalene degradation, this study suggests that KT2442 (pNF142) suppressed the enrichment of indigenous naphthalene degraders. 相似文献
998.
The effects of short-term resistance training on endocrine function in men and women 总被引:6,自引:0,他引:6
William J. Kraemer Robert S. Staron Fredrick C. Hagerman Robert S. Hikida Andrew C. Fry Scott E. Gordon Bradley C. Nindl Lincoln A. Gothshalk Jeff S. Volek James O. Marx Robert U. Newton Keijo H?kkinen 《European journal of applied physiology and occupational physiology》1998,78(1):69-76
This investigation examined hormonal adaptations to acute resistance exercise and determined whether training adaptations
are observed within an 8-week period in untrained men and women. The protocol consisted of a 1-week pre-conditioning orientation
phase followed by 8 weeks of heavy resistance training. Three lower-limb exercises for the quadriceps femoris muscle group
(squat, leg press, knee extension) were performed twice a week (Monday and Friday) with every other Wednesday used for maximal
dynamic 1 RM strength testing. Blood samples were obtained pre-exercise (Pre-Ex), immediately post-exercise (IP), and 5 min
post-exercise (5-P) during the first week of training (T-1), after 6 weeks (T-2) and 8 weeks (T-3) of training to determine
blood concentrations of whole-blood lactate (LAC), serum total testosterone (TT), sex-hormone binding globulin (SHBG), cortisol
(CORT) and growth hormone (GH). Serum TT concentrations were significantly (P ≤ 0.05) higher for men at all time points measured. Men did not demonstrate an increase due to exercise until T-2. An increase
in pre-exercise concentrations of TT were observed both for men and women at T-2 and T-3. No differences were observed for
CORT between men and women; increases in CORT above pre-exercise values were observed for men at all training phases and at
T-2 and T-3 for women. A reduction in CORT concentrations at rest was observed both in men and women at T-3. Women demonstrated
higher pre-exercise GH values than men at all training phases; no changes with training were observed for GH concentrations.
Exercise-induced increases in GH above pre-exercise values were observed at all phases of training. Women demonstrated higher
serum concentrations of SHBG at all time points. No exercise-induced increases were observed in men over the training period
but women increased SHBG with exercise at T-3. SHBG concentrations in women were also significantly higher at T-2 and T-3
when compared to T-1 values. Increases in LAC concentrations due to exercise were observed both for men and women for all
training phases but no significant differences were observed with training. These data illustrate that untrained individuals
may exhibit early-phase endocrine adaptations during a resistance training program. These hormonal adaptations may influence
and help to mediate other adaptations in the nervous system and muscle fibers, which have been shown to be very responsive
in the early phase of strength adaptations with resistance training.
Accepted: 11 December 1997 相似文献
999.
1000.