全文获取类型
收费全文 | 4096篇 |
免费 | 380篇 |
国内免费 | 331篇 |
专业分类
4807篇 |
出版年
2024年 | 16篇 |
2023年 | 66篇 |
2022年 | 151篇 |
2021年 | 236篇 |
2020年 | 162篇 |
2019年 | 169篇 |
2018年 | 183篇 |
2017年 | 125篇 |
2016年 | 187篇 |
2015年 | 261篇 |
2014年 | 306篇 |
2013年 | 295篇 |
2012年 | 397篇 |
2011年 | 311篇 |
2010年 | 192篇 |
2009年 | 160篇 |
2008年 | 177篇 |
2007年 | 179篇 |
2006年 | 157篇 |
2005年 | 145篇 |
2004年 | 128篇 |
2003年 | 133篇 |
2002年 | 132篇 |
2001年 | 96篇 |
2000年 | 85篇 |
1999年 | 74篇 |
1998年 | 37篇 |
1997年 | 34篇 |
1996年 | 27篇 |
1995年 | 25篇 |
1994年 | 24篇 |
1993年 | 18篇 |
1992年 | 22篇 |
1991年 | 25篇 |
1990年 | 15篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1956年 | 1篇 |
1952年 | 2篇 |
排序方式: 共有4807条查询结果,搜索用时 15 毫秒
71.
Sex steroid changes during temperature‐induced gonadal differentiation were evaluated in the olive flounder, Paralichthys olivaceus. Larvae were reared at 21 ± 0.5°C, 24 ± 0.5°C and 28 ± 0.5°C from day 40 post‐hatching (dph) to 90 dph. The proportion of males was 61.1, 76.7, 87.8 and 47.8% in 21°C, 24°C, 28°C and in control groups, respectively. Gonadal differentiation was circa 65 dph, when fishes were a mean 39 mm total length (TL). The gonads developed faster when fishes were reared in higher temperatures. Radioimmunoassay (RIA) analyses indicated that the level of estradiol‐17β (E2) changed during the period of gonadal differentiation and peaked at an onset of ovarian differentiation in all groups. Compared with fish in control groups, the levels of E2 were lower in thermal‐treated groups, especially in the highest temperature groups. The present results indicate that E2 plays a major role in the process of ovarian differentiation, and suggest that temperature‐induced masculinization in P. olivaceus is mainly due to a decrease in the E2 level during the period of ovarian differentiation. 相似文献
72.
Zhengui Huang Kejiang Lin Qidong You 《Bioorganic & medicinal chemistry letters》2013,23(14):4166-4171
As increasing drug-resistance poses an emerging threat to public health, the development of novel antibacterial agents is critical. We developed a workflow consisting of various methods for de novo design. In the workflow, 2D-QSAR model based on molecular fingerprints was constructed to extract the bioactive molecular fingerprints from a data set of DNA–gyrase inhibitors with new structure and mechanism. These fingerprints were converted into molecular fragments which were recombined to generate compound library. The new compound library was virtually screened by LigandFit and Gold docking, and the results were further investigated by pharmacophore validation and binding mode analysis. The workflow successfully achieved a potential DNA–gyrase inhibitor. It could be applied to design more novel potential DNA–gyrase inhibitors and provide theoretical basis for further optimization of the hit compounds. 相似文献
73.
Xiaoke Guo Qian Yang Jing Xu Li Zhang Hongxi Chu Peng Yu Yingying Zhu Jinglian Wei Weilin Chen Yaozhong Zhang Xiaojin Zhang Haopeng Sun Yiqun Tang Qidong You 《Bioorganic & medicinal chemistry》2013,21(21):6466-6476
Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel is reported as an efficacious and safe target for the treatment of AF. In this paper, we designed and synthesized three series of compounds through modifying the lead compound RH01617 that was screened out by the pharmacophore model we reported earlier. All of the compounds were evaluated by the whole-patch lamp technology and most of them possessed potent inhibitory activities against Kv1.5. Compounds IIIi and IIIl were evaluated for the target selectivity as well as the pharmacodynamic effects in an isolated rat model. Due to the promising pharmacological behavior, compound IIIl deserves further pharmacodynamic and pharmacokinetic evaluations. 相似文献
74.
Background
GC content varies greatly between different genomic regions in many eukaryotes. In order to determine whether this organization named isochore organization influences gene expression patterns, the relationship between GC content and gene expression has been investigated in man and mouse. However, to date, this question is still a matter for debate. Among the avian species, chicken (Gallus gallus) is the best studied representative with a complete genome sequence. The distinctive features and organization of its sequence make it a good model to explore important issues in genome structure and evolution.Methods
Only nuclear genes with complete information on protein-coding sequence with no evidence of multiple-splicing forms were included in this study. Chicken protein coding sequences, complete mRNA sequences (or full length cDNA sequences), and 5′ untranslated region sequences (5′ UTR) were downloaded from Ensembl and chicken expression data originated from a previous work. Three indices i.e. expression level, expression breadth and maximum expression level were used to measure the expression pattern of a given gene. CpG islands were identified using hgTables of the UCSC Genome Browser. Correlation analysis between variables was performed by SAS Proprietary Software Release 8.1.Results
In chicken, the GC content of 5′ UTR is significantly and positively correlated with expression level, expression breadth, and maximum expression level, whereas that of coding sequences and introns and at the third coding position are negatively correlated with expression level and expression breadth, and not correlated with maximum expression level. These significant trends are independent of recombination rate, chromosome size and gene density. Furthermore, multiple linear regression analysis indicated that GC content in genes could explain approximately 10% of the variation in gene expression.Conclusions
GC content is significantly associated with gene expression pattern and could be one of the important regulation factors in the chicken genome. 相似文献75.
Wenyu Liang Lingxia Wang Yaping Zhang Xiaoting Lei Jia Yang Xiangrong You Chi-Lien Cheng Youwen Zhou Wei Chen 《Journal of applied phycology》2013,25(6):1709-1721
Nostoc flagelliforme is a terrestrial cyanobacterium species whose metabolism follows an obvious diurnal pattern. Diurnal changes at physiological and proteomic levels of N. flagelliforme were obtained. In the morning (7:00 H), net photosynthesis, dark respiration, as well as the activities of total Rubisco, nitrogenase, glutamine synthetase, SOD and CAT were comparatively high. All these physiological activities significantly decreased in the afternoon (13:00 H), and then slowly increased in the evening (19:00 H). Thirty-one differentially expressed proteins with a variety of important functions were reproducibly detected and identified over a diurnal cycle. These proteins were categorized according to their predicted functions into secretion and regulation (15.79 %), antioxidative processes (21.05 %), nitrogen metabolism (10.53 %), carbohydrate and energy metabolism (10.53 %), as well as cell division (2.63 %). The remaining proteins had unclassified/unknown functions (21.05 %) or were unidentified (18.42 %). The results suggested a metabolic shift from active (7:00 H) to quiescent (13:00 H) and then to active (19:00 H) over the diurnal cycle. The differential expression level of ferritin, Mn-CAT, SOD and Fe-SOD may serve as molecular markers for the diurnal metabolism in N. flagelliforme. 相似文献
76.
Wen Hou Yangchun Xie Xinxin Song Xiaofang Sun Michael T. Lotze Herbert J. Zeh III 《Autophagy》2016,12(8):1425-1428
Macroautophagy/autophagy is an evolutionarily conserved degradation pathway that maintains homeostasis. Ferroptosis, a novel form of regulated cell death, is characterized by a production of reactive oxygen species from accumulated iron and lipid peroxidation. However, the relationship between autophagy and ferroptosis at the genetic level remains unclear. Here, we demonstrated that autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 (nuclear receptor coactivator 4) was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis. Consistently, genetic inhibition of NCOA4 inhibited ferritin degradation and suppressed ferroptosis. In contrast, overexpression of NCOA4 increased ferritin degradation and promoted ferroptosis. These findings provide novel insight into the interplay between autophagy and regulated cell death. 相似文献
77.
Skin aging caused by intrinsic or extrinsic processes characterized with functional proteomics 下载免费PDF全文
Jia‐You Fang Pei‐Wen Wang Chun‐Hsun Huang Mu‐Hong Chen Yun‐Ru Wu Tai‐Long Pan 《Proteomics》2016,16(20):2718-2731
The skin provides protection against environmental stress. However, intrinsic and extrinsic aging causes significant alteration to skin structure and components, which subsequently impairs molecular characteristics and biochemical processes. Here, we have conducted an immunohistological investigation and established the proteome profiles on nude mice skin to verify the specific responses during aging caused by different factors. Our results showed that UVB‐elicited aging results in upregulation of proliferating cell nuclear antigen and strong oxidative damage in DNA, whereas chronological aging abolished epidermal cell growth and increased the expression of caspase‐14, as well as protein carbonylation. Network analysis indicated that the programmed skin aging activated the ubiquitin system and triggered obvious downregulation of 14‐3‐3 sigma, which might accelerate the loss of cell growth capacity. On the other hand, UVB stimulation enhanced inflammation and the risk of skin carcinogenesis. Collectively, functional proteomics could provide large‐scale investigation of the potent proteins and molecules that play important roles in skin subjected to both intrinsic and extrinsic aging. 相似文献
78.
Gary Alan Barclay Armstrong Meijiang Liao Zhipeng You Alexandra Lissouba Brian Edwin Chen Pierre Drapeau 《PloS one》2016,11(3)
The methodology for site-directed editing of single nucleotides in the vertebrate genome is of considerable interest for research in biology and medicine. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 type II (Cas9) system has emerged as a simple and inexpensive tool for editing genomic loci of interest in a variety of animal models. In zebrafish, error-prone non-homologous end joining (NHEJ) has been used as a simple method to disrupt gene function. We sought to develop a method to easily create site-specific SNPs in the zebrafish genome. Here, we report simple methodologies for using CRISPR/Cas9-mediated homology directed repair using single-stranded oligodeoxynucleotide donor templates (ssODN) for site-directed single nucleotide editing, for the first time in two disease-related genes, tardbp and fus. 相似文献
79.
80.
【目的】以淀粉为原料的乙醇发酵工艺仍然是当前燃料乙醇的主要生产方式。然而,一些原料中含有的果胶物质不仅降低了乙醇产率,而且会导致醪液粘度增大,从而会进一步影响传质和传热、增加设备负担等。构建能够自主降解果胶质的重组酿酒酵母并应用于燃料乙醇生产是值得探索的领域。【方法】论文将来源于黑曲霉的果胶酯酶基因克隆于α因子信号肽下游并通过酵母α-凝集素C-端蛋白的介导构建了在细胞表面锚定表达果胶酯酶的重组酿酒酵母PE。【结果】重组酵母的果胶酯酶表达水平达到2.6 U/g(菌体湿重),并进一步鉴定了重组果胶酯酶性质。以甘薯粉为原料的同步糖化发酵实验中,重组酵母PE的乙醇浓度和乙醇转化率分别达到95 g/L和88.1%,与出发菌株相比提高了2.2%。更重要的是,表面展示果胶酯酶能够显著降低发酵过程中的发酵液粘度。【结论】通过在工业酿酒酵母表面展示表达果胶酯酶不仅能够提高糖化酶等的作用效果和酿酒酵母的代谢能力,而且能够显著降低乙醇生产过程中发酵液的粘度,将对工业规模乙醇生产在降低设备负担、节约能耗方面具有一定的潜在价值。 相似文献