全文获取类型
收费全文 | 5529篇 |
免费 | 400篇 |
国内免费 | 2篇 |
出版年
2023年 | 33篇 |
2022年 | 84篇 |
2021年 | 157篇 |
2020年 | 102篇 |
2019年 | 132篇 |
2018年 | 184篇 |
2017年 | 136篇 |
2016年 | 188篇 |
2015年 | 292篇 |
2014年 | 315篇 |
2013年 | 382篇 |
2012年 | 464篇 |
2011年 | 448篇 |
2010年 | 262篇 |
2009年 | 242篇 |
2008年 | 295篇 |
2007年 | 288篇 |
2006年 | 256篇 |
2005年 | 257篇 |
2004年 | 237篇 |
2003年 | 202篇 |
2002年 | 195篇 |
2001年 | 80篇 |
2000年 | 63篇 |
1999年 | 54篇 |
1998年 | 48篇 |
1997年 | 36篇 |
1996年 | 26篇 |
1995年 | 26篇 |
1994年 | 29篇 |
1993年 | 38篇 |
1992年 | 43篇 |
1991年 | 33篇 |
1990年 | 30篇 |
1989年 | 30篇 |
1988年 | 24篇 |
1987年 | 21篇 |
1986年 | 19篇 |
1985年 | 25篇 |
1984年 | 21篇 |
1983年 | 20篇 |
1982年 | 11篇 |
1981年 | 17篇 |
1980年 | 11篇 |
1979年 | 10篇 |
1978年 | 9篇 |
1976年 | 6篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1971年 | 5篇 |
排序方式: 共有5931条查询结果,搜索用时 484 毫秒
951.
952.
Diego La Mendola Serena Caminati Salvatore S. Emmi Giuseppe Maccarrone Adriana Pietropaolo 《Journal of inorganic biochemistry》2009,103(2):195-204
Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies were carried out on copper(II) complexes with chicken prion protein N-terminal fragments, Ac-(PHNPGY)4-NH2, and the mutated residue, Ac-(PHNPGF)4-NH2, to assess the role of tyrosine in the copper coordination. Both thermodynamic and spectroscopic results indicate that chicken prion fragments are not able to bind more than two copper ions and only with the involvement of side chain tyrosine groups. The prevailing complex shows one copper ion bound to four imidazole nitrogen atoms in the 1:1 metal to ligand ratio systems. The superoxide dismutase (SOD)-like activity of copper(II) complexes with the avian peptides and mammal analogue, Ac-(PHGGGWGQ)4-NH2, was also investigated by means of Pulse radiolysis. The copper(II) complexes with avian peptides do not display SOD-like activity, while very low activity has been detected for the copper(II) complexes with mammalian tetraoctarepeat. 相似文献
953.
Flávia de Castro Pereira Cesar Augusto Sam Tiago Vilanova-Costa Aliny Pereira de Lima Alessandra de Santana Braga Barbosa Ribeiro Hugo Delleon da Silva Luiz Alfredo Pavanin Elisângela de Paula Silveira-Lacerda 《Biological trace element research》2009,128(3):258-268
Ruthenium complexes have attracted much attention as possible building blocks for new transition-metal-based antitumor agents.
The present study examines the mitotoxic and clastogenic effects induced in the root tips of Allium cepa by cis-tetraammine(oxalato)ruthenium(III) dithionate {cis-[Ru(C2O2)(NH3)4]2(S2O6)} at different exposure durations and concentrations. Correlation tests were performed to determine the effects of the time
of exposure and concentration of ruthenium complex on mitotic index (MI) and mitotic aberration index. A comparison of MI
results of cis-[Ru(C2O2)(NH3)4]2(S2O6) to those of lead nitrate reveals that the ruthenium complex demonstrates an average mitotic inhibition eightfold higher
than lead, with the frequency of cellular abnormalities almost fourfold lower and mitotic aberration threefold lower. A. cepa root cells exposed to a range of ruthenium complex concentrations did not display significant clastogenic effects. Cis-tetraammine(oxalato)ruthenium(III) dithionate therefore exhibits a remarkable capacity to inhibit mitosis, perhaps by inhibiting
DNA synthesis or blocking the cell cycle in the G2 phase. Further investigation of the mechanisms of action of this ruthenium
complex will be important to define its clinical potential and to contribute to a novel and rational approach to developing
a new metal-based drug with antitumor properties complementary to those exhibited by the drugs already in clinical use. 相似文献
954.
Adriana Szmidt-Jaworska Krzysztof Jaworski Jan Kopcewicz 《Plant Growth Regulation》2009,57(2):115-126
It was revealed that cGMP is involved in the control of photoperiodic flower induction. Further insight into the signalling
function of cGMP is likely to be obtained by analysis of its effectors. Therefore, in the present study, we used various agents
that cause changes in cGMP-dependent kinase (PKG) activity and examined their effects on the activity of kinase isolated from
Pharbitis nil and flower induction. It was found that exogenous applications of PKG activators (cGMP, 8-pCPT-cGMP, 8-Br-cGMP, 8-pCPT-PET-cGMP)
to cotyledons which were exposed to a 12-h-long subinductive night significantly increased flowering response. From among
the many antagonists of cGMP-dependent protein kinase Rp-8-Br-PET-cGMPS, Rp-8-pCPT-cGMP and the synthetic heptapeptide inhibitor
of PKG were used for our analysis. When Rp-8-Br-PET-cGMPS and Rp-8-pCPT-cGMP were applied during a 16-h-long inductive night,
significant reduction in the number of flower buds was observed, whereas synthetic heptapeptide did not change the intensity
of flowering. The influence of the analysed chemicals on protein kinase activity was also examined in vitro. With the exception
of synthetic heptapeptide, which seems ineffective, the enzyme activity was stimulated by all agonists and significantly reduced
by all antagonists. The activity of protein kinase was assayed in P. nil soluble protein fractions from plants grown under flower-inducing and non-inducing conditions. In vitro phosphorylation was
slightly greater in the soluble fraction obtained from plants grown under the flower-inducing condition, reaching 1.05 nmol/min/mg
protein, when compared to the control 0.81 nmol/min/mg protein. In relation to the results described above, we can conclude
that cGMP as a mediator participating in photoperiodic flower induction may govern this process by the phosphorylation mechanism
via its influence on cGMP-dependent protein kinase activity. 相似文献
955.
Braulio M. Fraga Melchor G. Hernández Concepción Fernández José M.H. Santana 《Phytochemistry》2009,70(8):1038-1989
Nine taxa of the Sideritis genus, Sideritis argosphacelus var. spicata, Sideritis candicans var. eriocephala,Sideritis discolor, Sideritis kuegleriana, Sideritis lotsyi, Sideritis lotsyi var. mascaensis, Sideritis marmorea, Sideritis soluta and Sideritis tenoi, which are endemic from the Canary Islands, have been chemically studied. The diterpene sicanatriol 7β,18-diacetate was obtained from S.argosphacelus var. spicata, whilst a nor-diterpene, epiadejone, and the 3(2H)-benzofuranone solutin have been found in S. soluta. Another diterpene, sidendrodiol 18-monoacetate, has been isolated from S.argosphacelus var. spicata, for the first time as a natural product. Known sesquiterpenes, diterpenes, triterpenes, sterols, flavones, coumarins and other aromatic derivatives have also been isolated. These studies support the botanical division of the genus into two subgenera, Sideritis and Marrubiastrum, the three sections of the latter subgenus, Cretica, Empedocleopsis and Marrubiastrum, and the elevation of S. argosphacelus var. spicata, S. candicans var. eriocephala and S. lotsyi var. mascaensis to the rank of species. 相似文献
956.
Olga Mangoni Maria Saggiomo Monica Modigh Giulio Catalano Adriana Zingone Vincenzo Saggiomo 《Polar Biology》2009,32(3):311-323
The aim of this study was to assess the role of platelet ice microalgal communities in seeding pelagic blooms. Nutrient dynamics,
microalgal biomass, photosynthetic parameters, cell densities and species succession were studied in two mesocosm experiments,
designed to simulate the transition of microalgal communities from platelet ice habitat to pelagic conditions. The microalgal
assemblages were dominated by diatoms, 70% of which were benthic species such as Amphiprora kufferathii, Nitzschia stellata, and Berkeleya adeliensis. Photoacclimation of benthic species was inadequate also at relatively low irradiances. Exceptional growth capacity at different
light levels was observed for pelagic species such as Fragilariopsis cylindrus and Chaetoceros spp. which may be important in seeding blooms at ice breakup. Fragilariopsis cylindrus showed high growth rates both at 65 and 10% of incident light and in nutrient replete as well as in nutrient depleted conditions.
Five days after inoculation, phytoplankton biomass increased and nutrient concentrations decreased in both light conditions.
Nutrient uptake rates were up to 9.10 μmol L−1 d−1 of TIN in the high light tank and 6.18 μmol L−1 d−1 in the low light tank and nutrient depletion in the high light tank occurred 3 days prior to depletion in the low light tank.
At nutrient depletion, biomass concentrations were similar in both tanks, 30 and 34 μg Chla L−1.
This article belongs to a special topic: Five articles on Sea-ice communities in Terra Nova Bay (Ross Sea), coordinated by
L. Guglielmo and V. Saggiomo, appear in this issue of Polar Biology. The studies were conducted in the frame of the National
Program of Research in Antarctica (PNRA) of Italy. 相似文献
957.
Western lifestyle plays an important role in the prevalence of type 2 diabetes by causing insulin resistance and pancreatic
β-cell dysfunction, a prerequisite for the development of diabetes. High fat diet and alcohol are major components of the
western diet. The aim of the present study was to investigate the effects of ethanol and fatty acids on β-cell survival and
metabolism. We treated the rat β-cell line RINm5F with ethanol, a mixture of palmitic and oleic acids, or both. Reactive oxygen
species (ROS) were determined by (5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate) (CM-H2DCFDA) fluorescence
assay, and mitochondrial activity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction
assay and by determining ATP production. Cell viability was assessed with a cell counter and trypan blue exclusion, and the
mode of cell death by Hoechst33342 and propidium iodide staining. With both ethanol and fatty acid treatments, MTT reduction
and ATP production decreased, whereas ROS production increased. Ethanol treatment had no effect on cell number, whereas fatty
acid treatment reduced the cell number. Cell incubation with ethanol, fatty acids, or both increased the number of Hoechst
33342-positive nuclei. However, the majority of nuclei from fatty acid-treated cells were stained with propidium iodide, indicating
a loss of plasma membrane integrity. We conclude that both ethanol and fatty acids generate cellular oxidative stress, and
affect mitochondrial function in RINm5F β-cells. However, ethanol causes β-cell death by apoptosis, whereas fatty acids cause
cell death predominantly by necrosis. It is not known whether these results are applicable to human β-cells. 相似文献
958.
Xue Zhou Adriana Arita Thomas P. Ellen Xin Liu Jingxiang Bai John P. Rooney Adrienne D. Kurtz Catherine B. Klein Wei Dai Thomas J. Begley Max Costa 《Genomics》2009,94(5):294-307
We have used Saccharomyces cerevisiae to identify toxicologically important proteins and pathways involved in arsenic-induced toxicity and carcinogenicity in humans. We performed a systemic screen of the complete set of 4733 haploid S. cerevisiae single-gene-deletion mutants to identify those that have decreased or increased growth, relative to wild type, after exposure to sodium arsenite (NaAsO2). IC50 values for all mutants were determined to further validate our results. Ultimately we identified 248 mutants sensitive to arsenite and 5 mutants resistant to arsenite exposure. We analyzed the proteins corresponding to arsenite-sensitive mutants and determined that they belonged to functional categories that include protein binding, phosphate metabolism, vacuolar/lysosomal transport, protein targeting, sorting, and translocation, cell growth/morphogenesis, cell polarity and filament formation. Furthermore, these data were mapped onto a protein interactome to identify arsenite-toxicity-modulating networks. These networks are associated with the cytoskeleton, ubiquitination, histone acetylation and the MAPK signaling pathway. Our studies have potential implications for understanding toxicity and carcinogenesis in arsenic-induced human conditions, such as cancer and aging. 相似文献
959.
Noemi Baranda-Avila C. Adriana Mendoza-Rodríguez Sumiko Morimoto Elizabeth Langley Marco Cerbn 《The Journal of steroid biochemistry and molecular biology》2009,113(3-5):259-268
The rodent uterus is a widely studied target tissue for sexual steroid hormone action. The aim of the present study was to assess the molecular mechanism that participates in the initiation of cell proliferation of the rat uterine epithelial cells during the estrus (E)–metestrus (M) transition. Cell proliferation, ERα, c-fos, cyclin D1 and D3, cdk4, and cdk6 proteins were assessed in these animals by immunohistochemistry. Estradiol (E2) and progesterone (P4) plasma levels were assessed by RIA. The results indicate that the glandular epithelium starts to proliferate at 21:00 h on estrus day, and initiates at least 3 h before the luminal epithelium does. Fos expression was markedly increased during the afternoon of estrus day, and its increase was in parallel to ERα expression. Interestingly, both, cyclin D1 and D3 were abundantly expressed in the luminal and glandular epithelia, and nuclear immunolabelling of cyclin D1 and D3 precedes BrdU incorporation in the cell. cdk4 and cdk6 were localized in the nuclei in both epithelia throughout the studied time course. In addition, cdk4 was more abundant throughout estrus and metestrus days than cdk6. The overall results indicate that ERα, Fos and cyclins D1 and D3, cdk4 and cdk6 are expressed in both glandular and luminal epithelia of the rat uterus during the E–M transition. In conclusion, there is a good correlation between sequential expression of these proteins and cell cycle progression in the rat uterine epithelial cells during the estrous cycle. However, the differences observed in the cellular localization, time course of expression and the cellular types that express both cyclins between physiological and pharmacological conditions, demonstrated different mechanisms of regulation and should be due to the complex hormonal milieu during the estrous cycle. 相似文献
960.
Guido Achermann Theresa M. Ballard Francesca Blasco Pierre-Emmanuel Broutin Bernd Büttelmann Holger Fischer Martin Graf Maria-Clemencia Hernandez Peter Hilty Frédéric Knoflach Andreas Koblet Henner Knust Anke Kurt James R. Martin Raffaello Masciadri Richard H.P. Porter Heinz Stadler Andrew W. Thomas Gerhard Trube Jürgen Wichmann 《Bioorganic & medicinal chemistry letters》2009,19(19):5746-5752
Through iterative design cycles we have discovered a number of novel new classes where the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine was deemed the most promising GABAA α5 inverse agonist class with potential for cognitive enhancement. This class combines a modest subtype binding selectivity with inverse agonism and has the most favourable molecular properties for further lead optimisation towards a central nervous system (CNS) acting medicine. 相似文献