全文获取类型
收费全文 | 3636篇 |
免费 | 247篇 |
国内免费 | 3篇 |
专业分类
3886篇 |
出版年
2023年 | 25篇 |
2022年 | 44篇 |
2021年 | 87篇 |
2020年 | 60篇 |
2019年 | 82篇 |
2018年 | 106篇 |
2017年 | 90篇 |
2016年 | 130篇 |
2015年 | 177篇 |
2014年 | 163篇 |
2013年 | 240篇 |
2012年 | 225篇 |
2011年 | 228篇 |
2010年 | 157篇 |
2009年 | 146篇 |
2008年 | 170篇 |
2007年 | 153篇 |
2006年 | 165篇 |
2005年 | 130篇 |
2004年 | 137篇 |
2003年 | 108篇 |
2002年 | 113篇 |
2001年 | 87篇 |
2000年 | 77篇 |
1999年 | 78篇 |
1998年 | 29篇 |
1997年 | 32篇 |
1996年 | 27篇 |
1995年 | 37篇 |
1994年 | 22篇 |
1993年 | 27篇 |
1992年 | 39篇 |
1991年 | 42篇 |
1990年 | 33篇 |
1989年 | 37篇 |
1988年 | 32篇 |
1987年 | 33篇 |
1986年 | 40篇 |
1985年 | 26篇 |
1984年 | 14篇 |
1981年 | 17篇 |
1979年 | 19篇 |
1978年 | 17篇 |
1977年 | 17篇 |
1975年 | 16篇 |
1974年 | 23篇 |
1973年 | 16篇 |
1971年 | 11篇 |
1969年 | 13篇 |
1968年 | 14篇 |
排序方式: 共有3886条查询结果,搜索用时 15 毫秒
81.
82.
Jung Tak Park Mitsuo Kato Hang Yuan Nancy Castro Linda Lanting Mei Wang Rama Natarajan 《The Journal of biological chemistry》2013,288(31):22469-22480
Glomerular hypertrophy is a hallmark of diabetic nephropathy. Akt kinase activated by transforming growth factor-β1 (TGF-β) plays an important role in glomerular mesangial hypertrophy. However, the mechanisms of Akt activation by TGF-β are not fully understood. Recently, miR-200 and its target FOG2 were reported to regulate the activity of phosphatidylinositol 3-kinase (the upstream activator of Akt) in insulin signaling. Here, we show that TGF-β activates Akt in glomerular mesangial cells by inducing miR-200b and miR-200c, both of which target FOG2, an inhibitor of phosphatidylinositol 3-kinase activation. FOG2 expression was reduced in the glomeruli of diabetic mice as well as TGF-β-treated mouse mesangial cells (MMC). FOG2 knockdown by siRNAs in MMC activated Akt and increased the protein content/cell ratio suggesting hypertrophy. A significant increase of miR-200b/c levels was detected in diabetic mouse glomeruli and TGF-β-treated MMC. Transfection of MMC with miR-200b/c mimics significantly decreased the expression of FOG2. Conversely, miR-200b/c inhibitors attenuated TGF-β-induced decrease in FOG2 expression. Furthermore, miR-200b/c mimics increased the protein content/cell ratio, whereas miR-200b/c inhibitors abrogated the TGF-β-induced increase in protein content/cell. In addition, down-regulation of FOG2 by miR-200b/c could activate not only Akt but also ERK, which was also through PI3K activation. These data suggest a new mechanism for TGF-β-induced Akt activation through FOG2 down-regulation by miR-200b/c, which can lead to glomerular mesangial hypertrophy in the progression of diabetic nephropathy. 相似文献
83.
84.
Catarina Prado e Castro José Paulo Sousa María Isabel Arnaldos João Gaspar María Dolores García 《法国昆虫学会纪事》2013,49(1-2):128-139
The first forensic entomological study performed in Portugal is presented. Two piglet (Sus scrofa L.) carcasses were used to determine adult Calliphoridae activity on carrion over a period of 121 days, all along the end of spring and the summer, both in a shaded and a sunny site. Five decomposition stages were observed and a total of 10723 adult Calliphoridae, belonging to 11 species, were collected. Calliphora vicina, Calliphora vomitoria, Chrysomya albiceps and Lucilia caesar were the dominant species in this study. Decomposition was faster on the carcass exposed to the sun and the number of Calliphoridae specimens was higher there than in the shaded site. It was found a significant effect of the decomposition stage in the number of specimens attracted to the carcass, as well as a significant effect of the interaction between the decomposition stage and insolation regime. Calliphora and Lucilia species did not show preference for sunny or shaded areas. Important differences in the Calliphoridae community structure were found compared to other regions of the Iberian Peninsula, reinforcing the need of further studies in different environments and regions of this geographical area in order to collect information about the local necrophagous fauna used in forensic practice. 相似文献
85.
Marina Azevêdo Souza Susana Johann Luciana Alves Rodrigues dos Santos Lima Fernanda Fraga Campos Isolda Castro Mendes Heloisa Beraldo Elaine Maria de Souza-Fagundes Patrícia Silva Cisalpino Carlos Augusto Rosa Tania Maria de Almeida Alves Nívea Pereira de Sá Carlos Leomar Zani 《Memórias do Instituto Oswaldo Cruz》2013,108(3):342-351
Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes. 相似文献
86.
Post-fire coarse woody debris can represent a valuable nutrient reservoir for a regenerating ecosystem, helping to prevent soil fertility losses after a wildfire. However, there is scarce information on its effect on soil nutrient cycling and availability. We established three study sites along an altitudinal gradient in a burnt pine forest (SE Spain). At each site we determined: (1) decomposition rates and nutrient dynamics in charred logs left on the ground, 2 and 4 years after the fire, and (2) available nutrients in the soil and in the microbial fraction below charred logs and in bare soil areas. Despite the relatively slow decay rates in this Mediterranean climate (ca. 10 % of dry weight lost after 4 years), N and P were progressively released by logs, accounting for ca. 40 and 65 % of the initial content respectively after 4 years. This implies that the total aboveground biomass of the burnt forest released around 20 kg ha?1 of N and 2 kg ha?1 of P during this period. The presence of post fire coarse woody debris consistently increased soil organic matter by around 18 %, total C and N by 42 and 26 %, respectively, dissolved organic C and N by 47 %, available inorganic P by 68 %, and microbial biomass and nitrogen by some 36 and 48 %, respectively. By contrast, soil bulk density decreased by ca. 18 % under logs compared to bare areas. Thus, the fire-killed wood was useful in the recovery of soil fertility and nutrient availability. Leaving the post-fire woody debris on site can enhance the biogeochemical sustainability, microbiological processes and soil ecological functioning. The detrimental effect of post-fire salvage logging on soil fertility should be therefore considered when making management decisions. 相似文献
87.
Peanut plants exposed to water stress induced by polyethylene glycol (PEG) accumulated abscisic acid (ABA) and hydrogen peroxide (H2O2), the increase being significant at 12 and 24 h after addition, respectively. To address the question whether the increase in H2O2 production was related to ABA accumulation, the peanut leaves were pretreated with ABA biosynthesis inhibitor (sodium tungstate) and then exposed to water stress. Under these conditions, a decrease of ABA and H2O2 content were found after 12 h. The addition of 100 μM ABA restored H2O2 content reaching values similar to those under water stress at 12 h. We concluded that ABA accumulation is the first signal that triggers the H2O2 generation in peanut during first 12 h but its subsequent production is partially ABA-independent. 相似文献
88.
Miriam Andrés Mónica Bravo Maria Antonia Buil Marta Calbet Jordi Castro Teresa Domènech Peter Eichhorn Manel Ferrer Elena Gómez Martin D. Lehner Imma Moreno Richard S. Roberts Sara Sevilla 《Bioorganic & medicinal chemistry letters》2013,23(11):3349-3353
High throughput screening identified the pyrazole-4-acetic acid substructure as CRTh2 receptor antagonists. Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors. 相似文献
89.
Gisela A. Samaja Olga Castro Lautaro D. Alvarez María V. Dansey Daiana S. Escudero Adriana S. Veleiro Adalí Pecci Gerardo Burton 《Bioorganic & medicinal chemistry letters》2013,23(10):2893-2896
27-Nor-Δ4-dafachronic acid was prepared in nine steps and 14% overall yield by two sequential 2-carbon homologations from 20β-carboxyaldehyde-4-pregnen-3-one. Its activity was evaluated in vivo, where it rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants and restored their normal resistance to oxidative stress. 27-Nor-Δ4-dafachronic acid was also able to directly bind and activate DAF-12 in a transactivation cell-based luciferase reporter assay, although it was less active than the corresponding 25R-and 25S dafachronic acids. The binding mode of the 27-Nor steroid was studied by molecular dynamics using a homology model of the CeDAF-12 receptor. 相似文献
90.
Emilay B.T. Diogo Gleiston G. Dias Bernardo L. Rodrigues Tiago T. Guimarães Wagner O. Valença Celso A. Camara Ronaldo N. de Oliveira Mauro G. da Silva Vitor F. Ferreira Yen Galdino de Paiva Marilia O.F. Goulart Rubem F.S. Menna-Barreto Solange L. de Castro Eufrânio N. da Silva Júnior 《Bioorganic & medicinal chemistry》2013,21(21):6337-6348
In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17–24, 28–30 and 36–38 are described herein for the first time. Three of these novel compounds (28–30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 μM. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 μM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. 相似文献