全文获取类型
收费全文 | 1291篇 |
免费 | 93篇 |
专业分类
1384篇 |
出版年
2024年 | 4篇 |
2023年 | 16篇 |
2022年 | 21篇 |
2021年 | 53篇 |
2020年 | 25篇 |
2019年 | 32篇 |
2018年 | 38篇 |
2017年 | 26篇 |
2016年 | 40篇 |
2015年 | 76篇 |
2014年 | 69篇 |
2013年 | 93篇 |
2012年 | 112篇 |
2011年 | 121篇 |
2010年 | 67篇 |
2009年 | 74篇 |
2008年 | 93篇 |
2007年 | 76篇 |
2006年 | 71篇 |
2005年 | 58篇 |
2004年 | 50篇 |
2003年 | 45篇 |
2002年 | 36篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 13篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1987年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1969年 | 2篇 |
1967年 | 1篇 |
1962年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有1384条查询结果,搜索用时 15 毫秒
41.
Phylogeography of Y-chromosome haplogroup I reveals distinct domains of prehistoric gene flow in europe 总被引:12,自引:2,他引:12 下载免费PDF全文
Rootsi S Magri C Kivisild T Benuzzi G Help H Bermisheva M Kutuev I Barać L Pericić M Balanovsky O Pshenichnov A Dion D Grobei M Zhivotovsky LA Battaglia V Achilli A Al-Zahery N Parik J King R Cinnioğlu C Khusnutdinova E Rudan P Balanovska E Scheffrahn W Simonescu M Brehm A Goncalves R Rosa A Moisan JP Chaventre A Ferak V Füredi S Oefner PJ Shen P Beckman L Mikerezi I Terzić R Primorac D Cambon-Thomsen A Krumina A Torroni A Underhill PA Santachiara-Benerecetti AS Villems R Semino O 《American journal of human genetics》2004,75(1):128-137
To investigate which aspects of contemporary human Y-chromosome variation in Europe are characteristic of primary colonization, late-glacial expansions from refuge areas, Neolithic dispersals, or more recent events of gene flow, we have analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny that is widespread over Europe but virtually absent elsewhere. The analysis of 1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from 60 population samples, revealed several subclades with distinct geographic distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a rapidly decreasing frequency toward both the East European Plain and the Atlantic fringe, but microsatellite diversity reveals that France could be the source region of the early spread of both I1a and the less common I1c. Also, I1b*, which extends from the eastern Adriatic to eastern Europe and declines noticeably toward the southern Balkans and abruptly toward the periphery of northern Italy, probably diffused after the Last Glacial Maximum from a homeland in eastern Europe or the Balkans. In contrast, I1b2 most likely arose in southern France/Iberia. Similarly to the other subclades, it underwent a postglacial expansion and marked the human colonization of Sardinia ~9,000 years ago. 相似文献
42.
Protein kinase D (PKD) regulates many diverse cellular functions in response to diacylglycerol. To monitor PKD signaling in live cells, we generated a genetically encoded fluorescent reporter for PKD activity, DKAR (D kinase activity reporter). DKAR expressed in mammalian cells undergoes reversible fluorescence resonance energy transfer changes upon activation and inhibition of endogenous PKD. Surprisingly, we find that agonist-evoked activation of PKD is driven not only by diacylglycerol production, but by Ca(2+). Furthermore, elevation of intracellular Ca(2+), in the absence of any other stimulus, is sufficient to activate PKD. Concurrent imaging of Ca(2+), diacylglycerol, and PKD activity reveals that thapsigargin-mediated elevation of intracellular Ca(2+) is closely followed by a robust increase in diacylglycerol production, in turn followed by PKD activation. The Ca(2+)-induced production of diacylglycerol and accompanying PKD activation is dependent on phospholipase C activity. These data reveal that Ca(2+) is a major contributor to the initiation of PKD signaling through positive feedback regulation of diacylglycerol production, unveiling a new mechanism in PKD activation. 相似文献
43.
44.
Mikhova B Duddeck H Taskova R Mitova M Alipieva K 《Zeitschrift für Naturforschung. C, Journal of biosciences》2004,59(3-4):244-248
The aerial parts of Carthamus lanatus (Asteraceae) afforded four new oxygenated bisabolane fucosides, 10-hydroperoxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside, 11-hydro-peroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside, 10-hydroxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside and 11-hydroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside together with the known compounds a-bisabolol beta-D-fucopyranoside, asperuloside, sitosterol 3-O-beta-D-glucoside and stigmasterol 3-O-beta-D-glucoside. Asperuloside appears to be the second representative of the iridoid monoterpene group found in the plant family Asteraceae, which until recently was considered to lack iridoids. The main constituent a-bisabolol fucoside exhibited noticeable antibacterial and cytotoxic activities. 相似文献
45.
Maya JD Rodríguez A Pino L Pabón A Ferreira J Pavani M Repetto Y Morello A 《Biological research》2004,37(1):61-69
Proteins rich in sulfhydryl groups, such as metallothionein, are present in several strains of the parasite Trypanosoma cruzi, the etiological agent of Chagas' disease. Metallothionein-like protein concentrations ranged from 5.1 to 13.2 pmol/mg protein depending on the parasite strain and growth phase. Nifurtimox and benznidazole, used in the treatment of Chagas' disease, decreased metallothionein activity by approximately 70%. T. cruzi metallothionein was induced by ZnCl2. Metallothionein from T. cruzi was partially purified and its monobromobimane derivative showed a molecular weight of approximately 10,000 Da by SDS-PAGE analysis. The concentration of trypanothione, the major glutathione conjugate in T. cruzi, ranged from 3.8 to 10.8 nmol/mg protein, depending on the culture phase. The addition of buthionine sulfoximine to the protozoal culture considerably reduced the concentration of trypanothione and had no effect upon the metallothionein concentration. The possible contribution of metallothionein-like proteins to drug resistance in T. cruzi is discussed. 相似文献
46.
47.
Pérez-Melero C Maya AB del Rey B Peláez R Caballero E Medarde M 《Bioorganic & medicinal chemistry letters》2004,14(14):3771-3774
The 3-hydroxy-4-methoxyphenyl ring of combretastatin A-4 can be replaced by a 2-naphthyl moiety without significant loss of cytotoxicity and inhibition of tubulin polymerization potency. In this paper we show that the 6- or 7-quinolyl systems can in turn replace both cyclic moieties, keeping in the first case most of the potency as cytotoxic agent and in the second case as inhibitor of tubulin polymerization, related to the activities displayed by model compounds. 相似文献
48.
Altes A Ruiz A Barceló MJ Remacha AF Puig T Maya AJ Castell C Amate JM Saz Z Baiget M 《Genetic testing》2004,8(4):407-410
In Spain, 85% of patients with genetic hemochromatosis (GH) are homozygous for the C282Y mutation of the HFE gene. H63D and S65C mutations of HFE may also play some role in the disease. The aim of this study was to establish the prevalence of C282Y, H63D, and S65C mutations of the HFE gene in newborns in Catalonia, Spain. One thousand one hundred forty-six newborn screening cards were selected randomly. DNA from these cards was extracted and HFE mutations were analyzed with the LightCycler equipment (Roche Diagnostics Gmbh, Mannheim, Germany). Sufficient DNA sample was obtained to screen for the three mutations in 1,043 cases (91%). The allelic frequencies of C282Y, H63D, and S65C mutations were 0.03 (IC 95% 0.022-0.037), 0.2 (IC 95% 0.19-0.22), and 0.01 (95% confidence interval [CI] 0.006-0.015), respectively. The frequency of C282Y homozygous newborns was 0.001 (95% CI 0.0005-0.0014). The frequencies of newborns doubly heterozygous for C282Y/H63D and C282Y/S65C were 0.01 (95% CI 0.005-0.02) and 0.002 (95% CI 0.0002-0.01), respectively. The allelic frequency of C282Y mutation is similar to that observed in Southern France, in the Czech Republic and in some areas of Italy. The allelic frequency of H63D mutation in Catalonia is the highest reported to date. Nevertheless, S65C is infrequent. These data should be kept in mind when designing hemochromatosis genotypic screening programs in Catalonia. 相似文献
49.
Malignant peripheral nerve sheath tumors (MPNSTs) are characteristic of Neurofibromatosis type 1 (NF1), a human genetic disorder affecting approximately 1 in 3000 individuals. The absence of neurofibromin in Schwann cells results in hyperactivation of Ras, which contributes to Schwann cell hyperplasia. However, additional intracellular abnormalities in Schwann cells might contribute to the malignancy. We now report that cell lines derived from MPNSTs secrete elevated levels of prostaglandin E(2) (PGE(2)), express higher levels of phosphorylated mitogen-activated protein kinase (MAPK), phosphorylated cytosolic phospholipaseA(2) (cPLA(2)) and cyclooxygenase 2 (COX-2) when compared to normal adult human Schwann cells (nhSCs). PCR analysis reveals that NF1 MPNST cell lines express mRNA for both EP2 and EP4 prostaglandin E2 receptors, whereas nhSCs express only the EP4 receptor. COX-2 inhibitors and PGE(2) receptor antagonists decrease the proliferation of MPNST cell lines. These results indicate that prostaglandin metabolism is activated in MPNSTs and might contribute to tumor growth in NF1. 相似文献
50.
Tapia RA Salas C Morello A Maya JD Toro-Labbé A 《Bioorganic & medicinal chemistry》2004,12(9):2451-2458
The synthesis of dihydronaphthofurandione and dihydrofuroquinolinedione derivatives 4-11 was performed through Diels-Alder reactions of dihydrobenzofurandione 1 with several carbodienes and acrolein N,N-dimethylhydrazone. Then, the use of 5-bromobenzofurandione 2 toward 1,3-pentadiene and the 1-azadiene afforded quinones 6 and 11 with a total regioselectivity. All the prepared quinones were tested for trypanocidal activity in vitro against Trypanosoma epimastigotes, Tulahuen strain. Among the tested compounds, the furoquinolinediones 10 and 11 have shown potent trypanocidal activities but, only the 1,5-regioisomer (11) was found active as a redox cycling agent. Calculation of their stereoelectronic properties by the density-functional theory method provided a new insight for the trypanocidal activity of these heterocyclic quinones. 相似文献