全文获取类型
收费全文 | 22106篇 |
免费 | 1914篇 |
国内免费 | 61篇 |
专业分类
24081篇 |
出版年
2022年 | 158篇 |
2021年 | 252篇 |
2020年 | 151篇 |
2019年 | 220篇 |
2018年 | 257篇 |
2017年 | 221篇 |
2016年 | 358篇 |
2015年 | 664篇 |
2014年 | 715篇 |
2013年 | 1097篇 |
2012年 | 1197篇 |
2011年 | 1232篇 |
2010年 | 763篇 |
2009年 | 720篇 |
2008年 | 1134篇 |
2007年 | 1161篇 |
2006年 | 1071篇 |
2005年 | 1073篇 |
2004年 | 1001篇 |
2003年 | 978篇 |
2002年 | 950篇 |
2001年 | 259篇 |
2000年 | 229篇 |
1999年 | 299篇 |
1998年 | 289篇 |
1997年 | 207篇 |
1996年 | 215篇 |
1995年 | 190篇 |
1994年 | 209篇 |
1993年 | 181篇 |
1992年 | 202篇 |
1991年 | 195篇 |
1990年 | 177篇 |
1989年 | 183篇 |
1988年 | 204篇 |
1987年 | 188篇 |
1986年 | 163篇 |
1985年 | 207篇 |
1984年 | 222篇 |
1983年 | 211篇 |
1982年 | 217篇 |
1981年 | 265篇 |
1980年 | 226篇 |
1979年 | 180篇 |
1978年 | 210篇 |
1977年 | 184篇 |
1976年 | 158篇 |
1975年 | 175篇 |
1974年 | 181篇 |
1973年 | 175篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Andrew C. Stainthorpe J. Colin Murrell George P. C. Salmond Howard Dalton Veronica Lees 《Archives of microbiology》1989,152(2):154-159
Methane monooxygenase (MMO) is the enzyme responsible for the conversion of methane to methanol in methanotrophic bacteria. In addition, this enzyme complex oxidizes a wide range of aliphatic and aromatic compounds in a number of potentially useful biotransformations. In this study, we have used biochemical data obtained from purification and characterization of the soluble MMO from Methylococcus capsulatus (Bath), to identify structural genes encoding this enzyme by oligonucleotide probing. The genes encoding the and subunits of MMO were found to be chromosomally located and were linked in this organism. We report here on the analysis of a recombinant plasmid containing 12 kilobases of Methylococcus DNA and provide the first evidence for the localization and linkage of genes encoding the methane monooxygenase enzyme complex. DNA sequence analysis suggests that the primary structures of the and subunit of MMO are completely novel and the complete sequence of these genes is presented. 相似文献
992.
Keith C. White Patricia C. Babbitt Douglas D. Buechter George L. Kenyon 《Journal of Protein Chemistry》1992,11(5):489-494
The importance of creatine kinase (E.C. 2.7.3.2) in endocrine tissues has been generally overlooked. Using a specific radiometric assay, we have demonstrated the existence of CK in the Brockmann body (principal islet) of the Coho salmon. We have purified this protein from insular tissue and concurrently purified CK from brain and muscle of the salmon. Purification characteristics, immunological cross-reactivity, and N-terminal sequence analysis have demonstrated that the predominant cytosolic CK from the Brockmann body is indistinguishable from the BB (brain) isoenzyme. Immunocytochemical studies indicated that the enzyme resides in the endocrine parenchyma. Phosphocreatine may serve as a reservoir of energy in the islet and augment its capacity to secrete hormones. The induction of CK-BB in the islet by other hormones could influence the secretion of insular hormones. Interorgan flux of the substrate creatine may be an undescribed mechanism of physiological regulation. 相似文献
993.
George E. Halkos Nickolaos G. Tzeremes Stavros A. Kourtzidis 《Journal of Industrial Ecology》2016,20(5):1159-1175
In this article, we apply an additive two‐stage data envelopment analysis estimator on a panel of 20 countries with advanced economies for the time period 1990–2011 in order to create a composite sustainability efficiency index. We use a window‐based approach in order to study the countries over the years. The sustainability efficiency index is decomposed into production efficiency and eco‐efficiency indicators. The results reveal inequalities among the examined countries between the two stages. The eco‐efficiency stage is characterized by large inequalities among countries and significantly lower efficiency scores than the overall sustainability efficiency and the production efficiency. Finally, it is reported that a country's high production efficiency level does not ensure a high eco‐efficiency performance. 相似文献
994.
Rinat Sharir Jonathan Semo Sara Shimoni Tamar Ben-Mordechai Natalie Landa-Rouben Sofia Maysel-Auslender Aviv Shaish Michal Entin–Meer Gad Keren Jacob George 《PloS one》2014,9(12)
Background
Ischemic cardiac damage is associated with upregulation of cardiac pro-inflammatory cytokines, as well as invasion of lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We sought to determine whether the Treg pool is influenced by myocardial damage and whether Tregs transfer and deletion affect cardiac remodeling.Methods and Results
The number and functional suppressive activity of Tregs were assayed in mice subjected to experimental myocardial infarction. The numbers of splenocyte-derived Tregs in the ischemic mice were significantly higher after the injury than in the controls, and their suppressive properties were significantly compromised. Compared with PBS, adoptive Treg transfer to mice with experimental infarction reduced infarct size and improved LV remodeling and functional performance by echocardiography. Treg deletion with blocking anti-CD25 antibodies did not influence infarct size or echocardiographic features of cardiac remodeling.Conclusion
Treg numbers are increased whereas their function is compromised in mice with that underwent experimental infarction. Transfer of exogeneous Tregs results in attenuation of myocardial remodeling whereas their ablation has no effect. Thus, Tregs may serve as interesting potential interventional targets for attenuating left ventricular remodeling. 相似文献995.
Wei Chen George Lewith Li-qiong Wang Jun Ren Wen-jing Xiong Fang Lu Jian-ping Liu 《PloS one》2014,9(10)
Objective
Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the ‘China national essential drug list’ by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation.Methods
We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the ‘China national essential drug list’ for common cold. There was no restriction on study design.Results
A total of 33 CPHMs were listed in ‘China national essential drug list 2012’ for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality.Conclusions
The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs. 相似文献996.
Ourania N. Kostopoulou Ekaterini C. Kouvela George E. Magoulas Thomas Garnelis Ioannis Panagoulias Maria Rodi Georgios Papadopoulos Athanasia Mouzaki George P. Dinos Dionissios Papaioannou Dimitrios L. Kalpaxis 《Nucleic acids research》2014,42(13):8621-8634
Chloramphenicol (CAM) is a broad-spectrum antibiotic, limited to occasional only use in developed countries because of its potential toxicity. To explore the influence of polyamines on the uptake and activity of CAM into cells, a series of polyamine–CAM conjugates were synthesized. Both polyamine architecture and the position of CAM-scaffold substitution were crucial in augmenting the antibacterial and anticancer potency of the synthesized conjugates. Compounds 4 and 5, prepared by replacement of dichloro-acetyl group of CAM with succinic acid attached to N4 and N1 positions of N8,N8-dibenzylspermidine, respectively, exhibited higher activity than CAM in inhibiting the puromycin reaction in a bacterial cell-free system. Kinetic and footprinting analysis revealed that whereas the CAM-scaffold preserved its role in competing with the binding of aminoacyl-tRNA 3′-terminus to ribosomal A-site, the polyamine-tail could interfere with the rotatory motion of aminoacyl-tRNA 3′-terminus toward the P-site. Compared to CAM, compounds 4 and 5 exhibited comparable or improved antibacterial activity, particularly against CAM-resistant strains. Compound 4 also possessed enhanced toxicity against human cancer cells, and lower toxicity against healthy human cells. Thus, the designed conjugates proved to be suitable tools in investigating the ribosomal catalytic center plasticity and some of them exhibited greater efficacy than CAM itself. 相似文献
997.
George Boukouvalas Kyriaki Gerozissis Efthimia Kitraki 《Cellular and molecular neurobiology》2010,30(4):521-530
The peripubertal period is critical for the final maturation of circuits controlling energy homeostasis and stress response.
However, the consequence of juvenile fat consumption on adult physiology is not clear. This study analyzed the adult consequences
of post-weaning fat feeding on limbic–hypothalamic–pituitary–adrenal (HPA) axis components and on metabolic regulators of
female rats. Wistar rats were fed either a high fat (HF) diet or the normal chow from weaning to puberty or to 3 months of
age. Additional groups crossed their diets at puberty onset. Plasma leptin, insulin, and corticosterone levels were determined
by radioimmunoassay and their brain receptors by western blot analysis. Adult HF-fed animals though not overweight, had higher
corticosterone and reduced glucocorticoid receptor levels in the hypothalamus and hippocampus, compared to the controls. The
alterations in HPA axis emerged already at puberty onset. Leptin receptor levels in the hypothalamus were reduced only by
continuous fat feeding from weaning to adulthood. The pre-pubertal period appeared more vulnerable to diet-induced alterations
in adulthood than the post-pubertal one. Switching from fat diet to normal chow at puberty onset restored most of the diet-induced
alterations in the HPA axis. The corticosteroid circuit rather than the leptin or insulin system appears as the principal
target for the peripubertal fat diet-induced effects in adult female rats. 相似文献
998.
Constantin N. Baxevanis Angelos D. Gritzapis George V. Z. Dedoussis Nikolaos G. Papadopoulos Orestes Tsolas Michael Papamichail 《Cancer immunology, immunotherapy : CII》1994,38(4):281-286
We have recently demonstrated that prothymosin (ProT) when administered intraperitoneally (i.p.) protects DBA/2 mice against the growth of syngeneic leukemic L1210 cells through the induction of tumoricidal peritoneal cells producing high levels of tumor necrosis factor (TNF) [Papanastasiou et al. (1992) Cancer Immunol Immunother 35: 145]. In this report we tested further immunological alterations that may be caused by the administration of ProT in vivo. We demonstrate that i.p. injections of ProT enhance natural killer (NK) cell activity and induce lymphokine-activated (LAK) activity in vivo. Thus, splenocytes from ProT-treated DBA/2 animals exhibited significantly higher cytotoxic activity (up to threefold) against the NK-sensitive YAC cell line and the NK-resistant P815 and L1210 syngeneic tumor cells, as compared to splenocytes from syngeneic control mice. The enhancement of the cytotoxic profile of DBA/2 splenocytes was associated with increased percentages of CD8+ cells, NK cells and activated CD3+ cells. The ProT-induced effect persisted for 30 days after the end of the ProT treatment period and returned to normal levels 20 days later. SPlenocytes from non-treated DBA/2 animals generated high NK and LAK activities in response to ProT in vitro. The ProT-induced NK an LAK activities reached 84% and 75% respectively of what was obtained with interleukin-2 (IL-2). High concentrations of TNF and IL-2 were generated in response to ProT in LAK cultures. These findings suggest that ProT may provide an overall protective effect against tumor growth in vivo through induction of NK and LAK activities possibly indirectly via the production of IL-2 and TNF in the spleen, peritoneal cavity and probably other lymphoid organs.This work was supported by a CEC grant to M. Papamichail 相似文献
999.
Robert A. Mueller Thomas J. McCown Ricky D. Hunt Cecilia Lundberg George R. Breese 《Cellular and molecular neurobiology》1990,10(3):327-336
1. | Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. |
2. | Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. |
3. | It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells. |
1000.
Ruihan Zhang Xin Li Zhongjie Liang Kongkai Zhu Junyan Lu Xiangqian Kong Sisheng Ouyang Lin Li Yujun George Zheng Cheng Luo 《PloS one》2013,8(8)
Protein arginine methyltransferase 1 (PRMT1), the major arginine asymmetric dimethylation enzyme in mammals, is emerging as a potential drug target for cancer and cardiovascular disease. Understanding the catalytic mechanism of PRMT1 will facilitate inhibitor design. However, detailed mechanisms of the methyl transfer process and substrate deprotonation of PRMT1 remain unclear. In this study, we present a theoretical study on PRMT1 catalyzed arginine dimethylation by employing molecular dynamics (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) calculation. Ternary complex models, composed of PRMT1, peptide substrate, and S-adenosyl-methionine (AdoMet) as cofactor, were constructed and verified by 30-ns MD simulation. The snapshots selected from the MD trajectory were applied for the QM/MM calculation. The typical SN2-favored transition states of the first and second methyl transfers were identified from the potential energy profile. Deprotonation of substrate arginine occurs immediately after methyl transfer, and the carboxylate group of E144 acts as proton acceptor. Furthermore, natural bond orbital analysis and electrostatic potential calculation showed that E144 facilitates the charge redistribution during the reaction and reduces the energy barrier. In this study, we propose the detailed mechanism of PRMT1-catalyzed asymmetric dimethylation, which increases insight on the small-molecule effectors design, and enables further investigations into the physiological function of this family. 相似文献