全文获取类型
收费全文 | 4251篇 |
免费 | 413篇 |
专业分类
4664篇 |
出版年
2023年 | 49篇 |
2022年 | 98篇 |
2021年 | 151篇 |
2020年 | 120篇 |
2019年 | 117篇 |
2018年 | 105篇 |
2017年 | 93篇 |
2016年 | 160篇 |
2015年 | 321篇 |
2014年 | 313篇 |
2013年 | 309篇 |
2012年 | 375篇 |
2011年 | 391篇 |
2010年 | 195篇 |
2009年 | 139篇 |
2008年 | 193篇 |
2007年 | 183篇 |
2006年 | 155篇 |
2005年 | 153篇 |
2004年 | 96篇 |
2003年 | 92篇 |
2002年 | 105篇 |
2001年 | 30篇 |
2000年 | 32篇 |
1999年 | 46篇 |
1998年 | 29篇 |
1997年 | 28篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1993年 | 15篇 |
1992年 | 31篇 |
1991年 | 32篇 |
1990年 | 32篇 |
1988年 | 21篇 |
1987年 | 15篇 |
1986年 | 27篇 |
1985年 | 21篇 |
1984年 | 19篇 |
1983年 | 18篇 |
1982年 | 19篇 |
1981年 | 23篇 |
1980年 | 24篇 |
1977年 | 13篇 |
1975年 | 20篇 |
1974年 | 16篇 |
1973年 | 14篇 |
1972年 | 12篇 |
1970年 | 14篇 |
1969年 | 12篇 |
1967年 | 12篇 |
排序方式: 共有4664条查询结果,搜索用时 15 毫秒
161.
Lauren B.A. Woodruff Brian L. May Joseph R. Warner Ryan T. Gill 《Biotechnology and bioengineering》2013,110(5):1520-1526
In the genome‐engineering era, it is increasingly important that researchers have access to a common set of platform strains that can serve as debugged production chassis and the basis for applying new metabolic engineering strategies for modeling and characterizing flux, engineering complex traits, and optimizing overall performance. Here, we describe such a platform strain of E. coli engineered for ethanol production. Starting with a fully characterized host strain (BW25113), we site‐specifically integrated the genes required for homoethanol production under the control of a strong inducible promoter into the genome and deleted the genes encoding four enzymes from competing pathways. This strain is capable of producing >30 g/L of ethanol in minimal media with <2 g/L produced of any fermentative byproduct. Using this platform strain, we tested previously identified ethanol tolerance genes and found that while tolerance was improved under certain conditions, any effect on ethanol production or tolerance was lost when grown under production conditions. Thus, our findings reinforce the need for a metabolic engineering “commons” that could provide a set of platform strains for use in more sophisticated genome‐engineering strategies. Towards this end, we have made this production strain available to the scientific community. Biotechnol. Bioeng. 2013; 110: 1520–1526. © 2013 Wiley Periodicals, Inc. 相似文献
162.
Laura L. Yates Carsten Schnatwinkel Lee Hazelwood Lauren Chessum Anju Paudyal Helen Hilton M. Rosario Romero Jonathan Wilde Debora Bogani Jeremy Sanderson Caroline Formstone Jennifer N. Murdoch Lee A. Niswander Andy Greenfield Charlotte H. Dean 《Developmental biology》2013,373(2):267-280
During lung development, proper epithelial cell arrangements are critical for the formation of an arborized network of tubes. Each tube requires a lumen, the diameter of which must be tightly regulated to enable optimal lung function. Lung branching and lumen morphogenesis require close epithelial cell–cell contacts that are maintained as a result of adherens junctions, tight junctions and by intact apical–basal (A/B) polarity. However, the molecular mechanisms that maintain epithelial cohesion and lumen diameter in the mammalian lung are unknown. Here we show that Scribble, a protein implicated in planar cell polarity (PCP) signalling, is necessary for normal lung morphogenesis. Lungs of the Scrib mouse mutant Circletail (Crc) are abnormally shaped with fewer airways, and these airways often lack a visible, ‘open’ lumen. Mechanistically we show that Scrib genetically interacts with the core PCP gene Vangl2 in the developing lung and that the distribution of PCP pathway proteins and Rho mediated cytoskeletal modification is perturbed in ScribCrc/Crc lungs. However A/B polarity, which is disrupted in Drosophila Scrib mutants, is largely unaffected. Notably, we find that Scrib mediates functions not attributed to other PCP proteins in the lung. Specifically, Scrib localises to both adherens and tight junctions of lung epithelia and knockdown of Scrib in lung explants and organotypic cultures leads to reduced cohesion of lung epithelial cells. Live imaging of Scrib knockdown lungs shows that Scrib does not affect bud bifurcation, as previously shown for the PCP protein Celsr1, but is required to maintain epithelial cohesion. To understand the mechanism leading to reduced cell–cell association, we show that Scrib associates with β-catenin in embryonic lung and the sub-cellular distribution of adherens and tight junction proteins is perturbed in mutant lung epithelia. Our data reveal that Scrib is required for normal lung epithelial organisation and lumen morphogenesis by maintaining cell–cell contacts. Thus we reveal novel and important roles for Scrib in lung development operating via the PCP pathway, and in regulating junctional complexes and cell cohesion. 相似文献
163.
An individual's position in a social hierarchy profoundly affects behavior and physiology through interactions with community members, yet little is known about how the brain contributes to status differences between and within the social states or sexes. We aimed to determine sex-specific attributes of social status by comparing circulating sex steroid hormones and neural gene expression of sex steroid receptors in dominant and subordinate male and female Astatotilapia burtoni, a highly social African cichlid fish. We found that testosterone and 17β-estradiol levels are higher in males regardless of status and dominant individuals regardless of sex. Progesterone was found to be higher in dominant individuals regardless of sex. Based on pharmacological manipulations in males and females, progesterone appears to be a common mechanism for promoting courtship in dominant individuals. We also examined expression of androgen receptors, estrogen receptor α, and the progesterone receptor in five brain regions that are important for social behavior. Most of the differences in brain sex steroid receptor expression were due to sex rather than status. Our results suggest that the parvocellular preoptic area is a core region for mediating sex differences through androgen and estrogen receptor expression, whereas the progesterone receptor may mediate sex and status behaviors in the putative homologs of the nucleus accumbens and ventromedial hypothalamus. Overall our results suggest sex differences and similarities in the regulation of social dominance by gonadal hormones and their receptors in the brain. 相似文献
164.
Jonathan M. Rawson Richard H. Heineman Lauren B. Beach Jessica L. Martin Erica K. Schnettler Michael J. Dapp Steven E. Patterson Louis M. Mansky 《Bioorganic & medicinal chemistry》2013,21(22):7222-7228
The nucleoside analog 5,6-dihydro-5-aza-2′-deoxycytidine (KP-1212) has been investigated as a first-in-class lethal mutagen of human immunodeficiency virus type-1 (HIV-1). Since a prodrug monotherapy did not reduce viral loads in Phase II clinical trials, we tested if ribonucleotide reductase inhibitors (RNRIs) combined with KP-1212 would improve antiviral activity. KP-1212 potentiated the activity of gemcitabine and resveratrol and simultaneously increased the viral mutant frequency. G-to-C mutations predominated with the KP-1212-resveratrol combination. These observations represent the first demonstration of a mild anti-HIV-1 mutagen potentiating the antiretroviral activity of RNRIs and encourage the clinical translation of enhanced viral mutagenesis in treating HIV-1 infection. 相似文献
165.
Emily House Anthony Polwart Philippa Darbre Lester Barr George Metaxas Christopher Exley 《Journal of trace elements in medicine and biology》2013,27(4):257-266
The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content in defatted tissue and oil from such tissues and thereby contribute towards our knowledge on aluminium and any role in breast cancer. 相似文献
166.
167.
168.
Arkan Abadi Justin D. Crane Daniel Ogborn Bart Hettinga Mahmood Akhtar Andrew Stokl Lauren MacNeil Adeel Safdar Mark Tarnopolsky 《PloS one》2013,8(4)
Antioxidant supplements are widely consumed by the general public; however, their effects of on exercise performance are controversial. The aim of this study was to examine the effects of an antioxidant cocktail (α-lipoic acid, vitamin E and coenzyme Q10) on exercise performance, muscle function and training adaptations in mice. C57Bl/J6 mice were placed on antioxidant supplement or placebo-control diets (n = 36/group) and divided into trained (8 wks treadmill running) (n = 12/group) and untrained groups (n = 24/group). Antioxidant supplementation had no effect on the running performance of trained mice nor did it affect training adaptations; however, untrained female mice that received antioxidants performed significantly better than placebo-control mice (p ≤ 0.05). Furthermore, antioxidant-supplemented females (untrained) showed elevated respiratory capacity in freshly excised muscle fibers (quadriceps femoris) (p ≤ 0.05), reduced oxidative damage to muscle proteins (p ≤ 0.05), and increased expression of mitochondrial proteins (p ≤ 0.05) compared to placebo-controls. These changes were attributed to increased expression of proliferator-activated receptor gamma coactivator 1α (PGC-1α) (p ≤ 0.05) via activation of AMP-activated protein kinase (AMPK) (p ≤ 0.05) by antioxidant supplementation. Overall, these results indicate that this antioxidant supplement exerts gender specific effects; augmenting performance and mitochondrial function in untrained females, but does not attenuate training adaptations. 相似文献
169.
Se Li Lynn Rosenberg Julie R. Palmer Ghasi S. Phillips Linda J. Heffner Lauren A. Wise 《Obesity (Silver Spring, Md.)》2013,21(1):178-184
Objective:
Previous studies have consistently identified maternal obesity and gestational weight gain (GWG) as risk factors for macrosomia, but little is known about the effects of central adiposity and body fat distribution. Using self‐reported data from the Black Women's Health Study (BWHS), a large follow‐up study of US black women, we examined the risk of macrosomia in relation to prepregnancy waist circumference, prepregnancy waist‐to‐hip ratio (WHR), prepregnancy BMI, and GWG.Design and Methods:
During 1995–2003, BWHS participants ages 21–44 years delivered 6,687 full‐term singleton births (gestational age >37 weeks). We compared mothers of 691 infants weighing ≥4,000 g with mothers of 5,996 infants weighing <4,000 g. Generalized estimating equation models (GEE) that accounted for more than one birth per mother were used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI).Results:
Independent of prepregnancy BMI, prepregnancy waist circumference was positively associated with risk of macrosomia (OR = 1.58, 95% CI: 1.07–2.32, for ≥35.0 vs. <27.0 inches (≥88.9 vs. <68.6 cm); P trend = 0.04). As expected, prepregnancy BMI was also positively associated with macrosomia (OR = 1.74, 95% CI: 1.25–2.41 for BMI ≥35.0 vs. 18.5–24.9 kg m?2). GWG above the amount recommended by the 2009 Institute of Medicine report was associated with an increased risk of macrosomia and the association was present in each category of prepregnancy BMI (18.5–24.9, 25.0–29.9, and ≥30.0 kg m?2; P trend <0.001).Conclusions:
Our data suggest that overall obesity, high GWG, and high waist circumference are independent risk factors for macrosomia among US black women.170.