全文获取类型
收费全文 | 2856篇 |
免费 | 253篇 |
国内免费 | 1篇 |
专业分类
3110篇 |
出版年
2023年 | 10篇 |
2022年 | 22篇 |
2021年 | 36篇 |
2020年 | 15篇 |
2019年 | 29篇 |
2018年 | 24篇 |
2017年 | 35篇 |
2016年 | 60篇 |
2015年 | 126篇 |
2014年 | 122篇 |
2013年 | 199篇 |
2012年 | 208篇 |
2011年 | 197篇 |
2010年 | 130篇 |
2009年 | 109篇 |
2008年 | 165篇 |
2007年 | 162篇 |
2006年 | 183篇 |
2005年 | 186篇 |
2004年 | 180篇 |
2003年 | 148篇 |
2002年 | 151篇 |
2001年 | 54篇 |
2000年 | 32篇 |
1999年 | 60篇 |
1998年 | 49篇 |
1997年 | 23篇 |
1996年 | 25篇 |
1995年 | 30篇 |
1994年 | 23篇 |
1993年 | 30篇 |
1992年 | 22篇 |
1991年 | 16篇 |
1990年 | 19篇 |
1989年 | 27篇 |
1988年 | 18篇 |
1987年 | 11篇 |
1986年 | 11篇 |
1985年 | 11篇 |
1984年 | 26篇 |
1983年 | 16篇 |
1982年 | 14篇 |
1981年 | 16篇 |
1980年 | 10篇 |
1979年 | 9篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1974年 | 8篇 |
排序方式: 共有3110条查询结果,搜索用时 15 毫秒
71.
72.
Sarah K. Wendel Caroline E. Mullis Susan H. Eshleman Joel N. Blankson Richard D. Moore Jeanne C. Keruly Ron Brookmeyer Thomas C. Quinn Oliver Laeyendecker 《PloS one》2013,8(2)
Background
Viral suppression and viral breakthrough impact the humoral immune response to HIV infection. We evaluated the impact of viral suppression and viral breakthrough on results obtained with two cross-sectional HIV incidence assays.Methods
All samples were collected from adults in the US who were HIV infected for >2 years. Samples were tested with the BED capture enzyme immunoassay (BED-CEIA) which measures the proportion of IgG that is HIV-specific, and with an antibody avidity assay based on the Genetic Systems 1/2+ O ELISA. We tested 281 samples: (1) 30 samples from 18 patients with natural control of HIV-1 infection known as elite controllers or suppressors (2) 72 samples from 18 adults on antiretroviral therapy (ART), with 1 sample before and 2–6 samples after ART initiation, and (3) 179 samples from 20 virally-suppressed adults who had evidence of viral breakthrough receiving ART (>400 copies/ml HIV RNA) and with subsequent viral suppression.Results
For elite suppressors, 10/18 had BED-CEIA values <0.8 normalized optical density units (OD-n) and these values did not change significantly over time. For patients receiving ART, 14/18 had BED-CEIA values that decreased over time, with a median decrease of 0.42 OD-n (range 0.10 to 0.63)/time point receiving ART. Three patterns of BED-CEIA values were observed during viral breakthrough: (1) values that increased then returned to pre-breakthrough values when viral suppression was re-established, (2) values that increased after viral breakthrough, and (3) values that did not change with viral breakthrough.Conclusions
Viral suppression and viral breakthrough were associated with changes in BED-CEIA values, reflecting changes in the proportion of HIV-specific IgG. These changes can result in misclassification of patients with long-term HIV infection as recently infected using the BED-CEIA, thereby influencing a falsely high value for cross-sectional incidence estimates. 相似文献73.
Spatial and Temporal Biogeography of Soil Microbial Communities in Arid and Semiarid Regions 总被引:1,自引:0,他引:1
Zohar Pasternak Ashraf Al-Ashhab Joao Gatica Ron Gafny Shlomit Avraham Dror Minz Osnat Gillor Edouard Jurkevitch 《PloS one》2013,8(7)
Microbial communities in soils may change in accordance with distance, season, climate, soil texture and other environmental parameters. Microbial diversity patterns have been extensively surveyed in temperate regions, but few such studies attempted to address them with respect to spatial and temporal scales and their correlations to environmental factors, especially in arid ecosystems. In order to fill this gap on a regional scale, the molecular fingerprints and abundance of three taxonomic groups – Bacteria, α-Proteobacteria and Actinobacteria – were sampled from soils 0.5–100 km apart in arid, semi-arid, dry Mediterranean and shoreline Mediterranean regions in Israel. Additionally, on a local scale, the molecular fingerprints of three taxonomic groups – Bacteria, Archaea and Fungi – were sampled from soils 1 cm–500 m apart in the semi-arid region, in both summer and winter. Fingerprints of the Bacteria differentiated between all regions (P<0.02), while those of the α-Proteobacteria differentiated between some of the regions (0.01<P<0.09), and actinobacterial fingerprints were similar among all regions (P>0.05). Locally, fingerprints of archaea and fungi did not display distance-decay relationships (P>0.13), that is, the dissimilarity between communities did not increase with geographic distance. Neither was this phenomenon evident in bacterial samples in summer (P>0.24); in winter, however, differences between bacterial communities significantly increased as the geographic distances between them grew (P<0.01). Microbial community structures, as well as microbial abundance, were both significantly correlated to precipitation and soil characteristics: texture, organic matter and water content (R2>0.60, P<0.01). We conclude that on the whole, microbial biogeography in arid and semi-arid soils in Israel is determined more by specific environmental factors than geographic distances and spatial distribution patterns. 相似文献
74.
Context
Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.Methods
Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21), fatty acid binding protein-4 (FABP4), lipocalin-2 and plasminogen activator factor-1 (PAI1) were assessed. Statistics were performed by repeated measures ANOVA.Results
Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05). Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001) and adiponectin was also elevated at day 28 (P=0.001). FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.Conclusion
Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state. Clinical trial registration: www.clinicaltrials.gov (NCT00562393) 相似文献75.
Vincenzo Carbone Linley R. Schofield Amy K. Beattie Andrew J. Sutherland‐Smith Ron S. Ronimus 《Proteins》2013,81(11):2064-2070
Methenyltetrahydromethanopterin cyclohydrolase (Mch) is involved in the methanogenesis pathway of archaea as a C1 unit carrier where N5‐formyl‐tetrahydromethanopterin is converted to methenyl‐tetrahydromethanopterin. Mch from Methanobrevibacter ruminantium was cloned, purified, crystallized and its crystal structure solved at 1.37 Å resolution. A biologically active trimer, the enzyme is composed of two domains including an N‐terminal domain of six α‐helices encompassing a series of four β‐sheets and a predominantly anti‐parallel β–sheet at the C‐terminus flanked on one side by α‐helices. Sequence and structural alignments have helped identify residues involved in substrate binding and trimer formation. Proteins 2013; 81:2064–2070. © 2013 Wiley Periodicals, Inc. 相似文献
76.
UV light irradiation is being increasingly applied as a primary process for water disinfection, effectively used for inactivation of suspended (planktonic) cells. In this study, the use of UV irradiation was evaluated as a pretreatment strategy to control biofouling. The objective of this research was to elucidate the relative effectiveness of various targeted UV wavelengths and a polychromatic spectrum on bacterial inactivation and biofilm control. In a model system using Pseudomonas aeruginosa, the inactivation spectra corresponded to the DNA absorption spectra for all wavelengths between 220 and 280 nm, while wavelengths between 254 nm and 270 nm were the most effective for bacterial inactivation. Similar wavelengths of 254-260-270 nm were also more effective for biofilm control in most cases than targeted 239 and 280 nm. In addition, the prevention of biofilm formation by P. aeruginosa with a full polychromatic lamp was UV dose-dependent. It appears that biofilm control is improved when larger UV doses are given, while higher levels of inactivation are obtained when using a full polychromatic MP lamp. However, no significant differences were found between biofilms produced by bacteria that survived UV irradiation and biofilms produced by control bacteria at the same microbial counts. Moreover, the experiments showed that biofilm prevention depends on the post-treatment incubation time and nutrient availability, in addition to targeted wavelengths, UV spectrum and UV dose. 相似文献
77.
Nabil Khattab Ron Johnston Tariq Modood Ibrahim Sirkeci 《Ethnic and racial studies》2013,36(9):1466-1481
This paper expands the existing literature on ethnicity and economic activity in Britain by studying the impact of religion and class. It argues that while the class location of the different South-Asian groups is important in determining their labour market outcomes, it does not operate independently from ethnicity; rather it is highly influenced by ethnicity in the process of determining the labour market participation of these groups. We use data obtained from the 2001 UK Census on Indian, Pakistani, and Bangladeshi men and women aged between twenty and twenty nine. Our findings confirm that class structure of the South-Asian groups is highly ethnicized, in that the ethno-religious background and class are interwoven to the extent that the separation between them is not easy, if not impossible. 相似文献
78.
A. Shirak Y. Palti O. Bern T. D. Kocher E. Gootwine E. Seroussi G. Hulata M. Ron R. R. Avtalion 《Journal of fish biology》2013,82(1):42-53
Offspring of a highly inbred gynogenetic line of Oreochromis aureus displayed 12‐fold increase in twinning rate compared to the outbred population. Asymmetric conjoined twins, which consist of a normal embryo attached to a malformed‐atrophic twin, were frequently encountered in both gynogenetic (90·7%) and outbred (38·2%) embryos. The monozygotic origin of these twins was determined using five microsatellite markers. Progeny of heterozygous parents for the microsatellite UNH159 were separated into sub‐sets of twins and normal full‐sibs. Consistent with previous reports, the normal embryo sub‐set exhibited elimination of both types of homozygotes for the UNH159 genetic marker at 2–8 days after fertilization. Unexpectedly, this elimination was less frequent in twins. The UNH159 marker as well as RNA‐binding motif protein, X‐linked (rbmx), SRY‐box containing gene 3 (sox3) and alpha‐thalassemia/mental retardation syndrome X‐linked (atrx) genes were mapped to linkage group 2. These gene orthologues are all located on the mammalian X chromosome and atrx is necessary for the X‐chromosome inactivation. 相似文献
79.
Kamila Chughtai Lu Jiang Tiffany R. Greenwood Kristine Glunde Ron M. A. Heeren 《Journal of lipid research》2013,54(2):333-344
The lipid compositions of different breast tumor microenvironments are largely unknown due to limitations in lipid imaging techniques. Imaging lipid distributions would enhance our understanding of processes occurring inside growing tumors, such as cancer cell proliferation, invasion, and metastasis. Recent developments in MALDI mass spectrometry imaging (MSI) enable rapid and specific detection of lipids directly from thin tissue sections. In this study, we performed multimodal imaging of acylcarnitines, phosphatidylcholines (PC), a lysophosphatidylcholine (LPC), and a sphingomyelin (SM) from different microenvironments of breast tumor xenograft models, which carried tdTomato red fluorescent protein as a hypoxia-response element-driven reporter gene. The MSI molecular lipid images revealed spatially heterogeneous lipid distributions within tumor tissue. Four of the most-abundant lipid species, namely PC(16:0/16:0), PC(16:0/18:1), PC(18:1/18:1), and PC(18:0/18:1), were localized in viable tumor regions, whereas LPC(16:0/0:0) was detected in necrotic tumor regions. We identified a heterogeneous distribution of palmitoylcarnitine, stearoylcarnitine, PC(16:0/22:1), and SM(d18:1/16:0) sodium adduct, which colocalized primarily with hypoxic tumor regions. For the first time, we have applied a multimodal imaging approach that has combined optical imaging and MALDI-MSI with ion mobility separation to spatially localize and structurally identify acylcarnitines and a variety of lipid species present in breast tumor xenograft models. 相似文献
80.
Marina Shenkman Bella Groisman Efrat Ron Edward Avezov Linda M. Hendershot Gerardo Z. Lederkremer 《The Journal of biological chemistry》2013,288(4):2167-2178
Studies of misfolded protein targeting to endoplasmic reticulum-associated degradation (ERAD) have largely focused on glycoproteins, which include the bulk of the secretory proteins. Mechanisms of targeting of nonglycosylated proteins are less clear. Here, we studied three nonglycosylated proteins and analyzed their use of known glycoprotein quality control and ERAD components. Similar to an established glycosylated ERAD substrate, the uncleaved precursor of asialoglycoprotein receptor H2a, its nonglycosylated mutant, makes use of calnexin, EDEM1, and HRD1, but only glycosylated H2a is a substrate for the cytosolic SCFFbs2 E3 ubiquitin ligase with lectin activity. Two nonglycosylated BiP substrates, NS-1κ light chain and truncated Igγ heavy chain, interact with the ERAD complex lectins OS-9 and XTP3-B and require EDEM1 for degradation. EDEM1 associates through a region outside of its mannosidase-like domain with the nonglycosylated proteins. Similar to glycosylated substrates, proteasomal inhibition induced accumulation of the nonglycosylated proteins and ERAD machinery in the endoplasmic reticulum-derived quality control compartment. Our results suggest a shared ERAD pathway for glycosylated and nonglycosylated proteins composed of luminal lectin machinery components also capable of protein-protein interactions. 相似文献