全文获取类型
收费全文 | 2160篇 |
免费 | 139篇 |
专业分类
2299篇 |
出版年
2023年 | 9篇 |
2022年 | 15篇 |
2021年 | 41篇 |
2020年 | 15篇 |
2019年 | 47篇 |
2018年 | 54篇 |
2017年 | 29篇 |
2016年 | 45篇 |
2015年 | 91篇 |
2014年 | 125篇 |
2013年 | 144篇 |
2012年 | 156篇 |
2011年 | 170篇 |
2010年 | 106篇 |
2009年 | 97篇 |
2008年 | 141篇 |
2007年 | 135篇 |
2006年 | 119篇 |
2005年 | 126篇 |
2004年 | 115篇 |
2003年 | 95篇 |
2002年 | 81篇 |
2001年 | 26篇 |
2000年 | 25篇 |
1999年 | 28篇 |
1998年 | 23篇 |
1997年 | 19篇 |
1996年 | 17篇 |
1995年 | 19篇 |
1994年 | 16篇 |
1993年 | 11篇 |
1992年 | 18篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 8篇 |
1977年 | 6篇 |
1975年 | 6篇 |
1974年 | 3篇 |
1972年 | 3篇 |
1968年 | 4篇 |
排序方式: 共有2299条查询结果,搜索用时 15 毫秒
11.
Gabriella M. Anic Vernon K. Sondak Jane L. Messina Neil A. Fenske Jonathan S. Zager Basil S. Cherpelis Ji-Hyun Lee William J. Fulp Pearlie K. Epling-Burnette Jong Y. Park Dana E. Rollison 《Cancer epidemiology》2013,37(4):434-439
Background: Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. Methods: Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. Results: Melanoma patients had longer telomeres than controls (odds ratio (OR) = 3.75; 95% confidence interval (CI): 2.02–6.94 for highest versus lowest tertile) (P for trend = <0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR = 0.01; 95% CI: 0.00–0.05 for highest versus lowest tertile) (P for trend = <0.0001) and BCC (OR = 0.10; 95% CI: 0.06–0.19 for highest versus lowest tertile) (P for trend = <0.0001). Conclusion: Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC. 相似文献
12.
In many species, including wheat, crossing over is distal, and the proximal regions of chromosome arms contribute little to
genetic maps. This was thought to be a consequence of terminal initiation of synapsis favoring distal crossing over. However,
in an inverted rye chromosome arm, the pattern of metaphase I chiasmata was also inverted, suggesting that crossover frequencies
were specific to chromosome segments. Here, wheat chromosome arms 2BS and 4AL, with essentially entire arms inverted in reverse
tandem duplications (rtd), were studied in the MI of meiosis. Inversion–duplication placed the recombining segments in the
middle of the arms. While the overall pairing frequencies of the inverted–duplicated arms were considerably reduced relative
to normal arms, chiasmata, if present, were always located in the same regions as in structurally normal arms, and relative
chiasma frequencies remained the same. The frequencies of fragment or fragment + bridge configurations in AI and AII indicated
that of the two tandemly arranged copies of segments in rtds, the more distal inverted segments were more likely to cross
over than the segments in their original orientations. These observations show that also in wheat, relative crossover frequencies
along chromosome arms are predetermined and independent of the segment location. The segments normally not licensed to cross
over do not do so even when placed in seemingly most favorable positions for it. 相似文献
13.
14.
Cartesio Favalli Peter Leport Bernard M. Jaffe M.Gabriella Santoro Thomas Simmet Vera Del Gobbo Enrico Garaci 《Cellular immunology》1982,72(2):351-359
The effect of 16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) on humoral and cellular immunoresponsiveness has been compared in normal mice and in mice immunosuppressed by splenectomy and thymectomy plus antithymocyte serum (ATS). Splenectomy resulted in immunosuppression manifested by augmentation of B-16 melanoma growth; this stimulatory effect was reversed by di-M-PGE2. In animals immunosuppressed by thymectomy plus ATS, di-M-PGE2 augmented the humoral and cellular immune responses; this was manifested by slowing of the growth of B-16 melanoma and by stimulating the number of plaque-forming cells, hemagglutinin titers, and delayed-hypersensitivity reactions to sheep erythrocytes. In contrast, in normal (nonthymectomized) mice, di-M-PGE2 was mildly immunosuppressive. Finally, adriamycin-immunosuppressed normal mice and this suppression were reversed by the addition of di-M-PGE2 to the treatment regimen. 相似文献
15.
Gestodene acidic treatment afforded a single rearrangement product, namely 13-beta-ethyl-18,19-dinorpregna-4,14,16-trien-3,20-dione 3, which was originated through HCl-catalyzed Rupe rearrangement. Drospirenone acidic treatment yielded two epimeric lactones by addition of HCl to the 6beta,7beta-cyclopropane ring, namely 7beta-(chloromethyl)-15beta,16beta-methylene-3-oxo-17beta-pregn-4-ene-21,17-carbolactone 4 and 7beta-(chloromethyl)-15beta,16beta-methylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactone 5. The structure of the compounds was assessed by spectroscopic and crystallographic methods. 相似文献
16.
Gabriella Juhasz Xenia Gonda Gabor Hullam Nora Eszlari David Kovacs Judit Lazary Dorottya Pap Peter Petschner Rebecca Elliott John Francis William Deakin Ian Muir Anderson Peter Antal Klaus-Peter Lesch Gyorgy Bagdy 《PloS one》2015,10(3)
Background
Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity.Methods
In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject. Besides traditional statistical analysis we calculated Bayesian effect strength and relevance of 5-HTTLPR genotypes in specified models.Results
The short (s) low expressing allele showed association with increased risk of depression related phenotypes, but all nominally significant effects would turn to non-significant after correction for multiple testing in the traditional analysis. Bayesian effect strength and relevance analysis, however, confirmed the role of 5-HTTLPR. Regarding current (BSI) and lifetime depression 5-HTTLPR-by-RLE interactions were confirmed. Main effect, with other words direct association, was supported with BSI anxiety. With more frequent RLE the prevalence or symptoms of depression increased in ss carriers. Although CHA failed to show an interaction with 5-HTTLPR, in young subjects CHA sensitized towards the depression promoting effect of even mild RLE. Furthermore, the direct association of anxiety with the s allele was driven by young (≤30) individuals.Limitations
Our study is cross-sectional and applies self-report questionnaires.Conclusions
Albeit 5-HTTLPR has only weak/moderate effects, the s allele is directly associated with anxiety and modulates development of depression in homogeneous subgroups. 相似文献17.
Gabriella Eliason Samy M Abdel-Halim Karin Piehl-Aulin Fawzi Kadi 《Respiratory research》2010,11(1):97
Background
It is hypothesized that decreased capillarization of limb skeletal muscle is implicated in the decreased exercise tolerance in COPD patients. We have recently demonstrated decreased number of capillaries per muscle fibre (CAF) but no changes in CAF in relation to fibre area (CAFA), which is based on the diffusion distance between the capillary and muscle fibre. The aim of the current study is to investigate the muscle-to-capillary interface which is an important factor involved in oxygen supply to the muscle that has previously been suggested to be a more sensitive marker for changes in the capillary bed compared to CAF and CAFA.Methods
23 COPD patients and 12 age-matched healthy subjects participated in the study. Muscle-to-capillary interface was assessed in muscle biopsies from the tibialis anterior muscle using the following parameters:1) The capillary-to-fibre ratio (C:Fi) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre2) The ratio between C:Fi and the fibre perimeter (CFPE-index)3) The ratio between length of capillary and fibre perimeter (LC/PF) which is also referred to as the index of tortuosity.Exercise capacity was determined using the 6-min walking test.Results
A positive correlation was found between CFPE-index and ascending disease severity with CFPE-index for type I fibres being significantly lower in patients with moderate and severe COPD. Furthermore, a positive correlation was observed between exercise capacity and CFPE-index for both type I and type IIa fibres.Conclusion
It can be concluded that the muscle-to-capillary interface is disturbed in the tibialis anterior muscle in patients with COPD and that interface is strongly correlated to increased disease severity and to decreased exercise capacity in this patient group. 相似文献18.
Marcos Fernando Basso Karoline Estefani Duarte Thais Ribeiro Santiago Wagner Rodrigo de Souza Bruno de Oliveira Garcia Brbara Dias Brito da Cunha Adilson Kenji Kobayashi Hugo Bruno Correa Molinari 《Plant Biotechnology》2021,38(2):227
The CRISPR/Cas9 system has been used for genome editing in several organisms, including higher plants. This system induces site-specific mutations in the genome based on the nucleotide sequence of engineered guide RNAs. The complex genomes of C4 grasses makes genome editing a challenge in key grass crops like maize (Zea mays), sorghum (Sorghum bicolor), Brachiaria spp., switchgrass (Panicum virgatum), and sugarcane (Saccharum spp.). Setaria viridis is a diploid C4 grass widely used as a model for these C4 crop plants. Here, an optimized CRISPR/Cas9 binary vector that exploits the non-homologous end joining (NHEJ) system was used to knockout a green fluorescent protein (gfp) transgene in S. viridis accession A10.1. Transformation of embryogenic callus by A. tumefaciens generated ten glufosinate-ammonium resistant transgenic events. In the T0 generation, 60% of the events were biallelic mutants in the gfp transgene with no detectable accumulation of GFP protein and without insertions or deletions in predicted off-target sites. The gfp mutations generated by CRISPR/Cas9 were stable and displayed Mendelian segregation in the T1 generation. Altogether, the system described here is a highly efficient genome editing system for S. viridis, an important model plant for functional genomics studies in C4 grasses. Also, this system is a potential tool for improvement of agronomic traits in C4 crop plants with complex genomes. 相似文献
19.
Coccetti P Zinzalla V Tedeschi G Russo GL Fantinato S Marin O Pinna LA Vanoni M Alberghina L 《Biochemical and biophysical research communications》2006,346(3):786-793
We have previously identified Ser201 of Sic1, a yeast cyclin-dependent kinase inhibitor, as an in vitro target of protein kinase CK2. Here we present new evidence, by using specific anti-P-Ser201 antibodies and 2-D gel electrophoresis coupled to MALDI mass spectrometry analysis, that Sic1 is phosphorylated in vivo on Ser201 shortly after its de novo synthesis, during late anaphase in glucose-grown cells. This phosphorylation is also detected in Sic1 immunopurified from G1 cells. In agreement with these data we also show that the catalytic alpha' subunit of CK2, whose function is required for cell cycle progression, is detected in Sic1 immunopurified complexes, and that phosphorylation on Ser201 is reduced after CK2 inactivation at the non-permissive temperature in a cka1delta cka2(ts) yeast strain. These data strongly support the notion that CK2 phosphorylates Sic1 in vivo. 相似文献
20.
HOTAIR role in melanoma progression and its identification in the blood of patients with advanced disease 下载免费PDF全文