全文获取类型
收费全文 | 6787篇 |
免费 | 404篇 |
国内免费 | 1篇 |
出版年
2022年 | 39篇 |
2021年 | 85篇 |
2020年 | 34篇 |
2019年 | 49篇 |
2018年 | 76篇 |
2017年 | 71篇 |
2016年 | 105篇 |
2015年 | 151篇 |
2014年 | 233篇 |
2013年 | 318篇 |
2012年 | 343篇 |
2011年 | 364篇 |
2010年 | 199篇 |
2009年 | 179篇 |
2008年 | 322篇 |
2007年 | 332篇 |
2006年 | 324篇 |
2005年 | 352篇 |
2004年 | 298篇 |
2003年 | 303篇 |
2002年 | 333篇 |
2001年 | 242篇 |
2000年 | 253篇 |
1999年 | 188篇 |
1998年 | 113篇 |
1997年 | 66篇 |
1996年 | 62篇 |
1995年 | 63篇 |
1994年 | 59篇 |
1993年 | 62篇 |
1992年 | 123篇 |
1991年 | 139篇 |
1990年 | 108篇 |
1989年 | 107篇 |
1988年 | 125篇 |
1987年 | 102篇 |
1986年 | 95篇 |
1985年 | 88篇 |
1984年 | 61篇 |
1983年 | 67篇 |
1982年 | 49篇 |
1981年 | 35篇 |
1980年 | 36篇 |
1979年 | 49篇 |
1978年 | 44篇 |
1976年 | 31篇 |
1975年 | 36篇 |
1974年 | 31篇 |
1973年 | 35篇 |
1971年 | 36篇 |
排序方式: 共有7192条查询结果,搜索用时 15 毫秒
951.
Fuchi N Iura Y Kaneko H Nitta A Suyama K Ueda H Yamaguchi S Nishimura K Fujii S Sekiya Y Yamada M Takahashi T 《Bioorganic & medicinal chemistry letters》2012,22(13):4358-4361
We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis. 相似文献
952.
T Taguchi T Ebihara A Furukawa Y Hidaka R Ariga S Okamoto K Ichinose 《Bioorganic & medicinal chemistry letters》2012,22(15):5041-5045
An oxygenated derivative of dihydrokalafungin (DHK) was isolated from a deletion mutant of the actVA-ORF4 gene involved in the biosynthesis of a dimeric benzoisochromanequinone (BIQ) antibiotic, actinorhodin (ACT), in Streptomyces coelicolor A3(2). Spectroscopic analysis elucidated its structure as 8-hydroxy-DHK, corresponding to the monomeric unit of ACT. Further metabolite analysis identified its related compound, clearly derived from the reduction of 8-hydroxy-DHK. The structures of these metabolites indicate the essential role of ActVA-ORF4 in ACT biosynthesis, specifically in dimerization of a BIQ intermediate via C-C bond formation. 相似文献
953.
Tsounapi P Saito M Dimitriadis F Kitatani K Kinoshita Y Shomori K Takenaka A Satoh K 《Life sciences》2012,90(17-18):649-656
AimsTo investigate the participation of KATP channels on the ischemia-reperfusion (IR)-induced apoptosis in the rat testis.Main methodsEight-week-old male Sprague–Dawley rats were divided into three groups: control and IR rats without or with cromakalim (300 μg/kg intraperitoneally), 30 min before the induction of ischemia. The right testicular artery and vein were clamped to induce ischemia in the testis. Sixty minutes after the ischemia, a 24 h period of reperfusion followed. Then, expressions of KIR6.1, KIR6.2, caspase-3, PARP, Fas, FasL, and KIR6.1 and KIR6.2 mRNAs were investigated by Western blot analyses and real-time PCR methods, respectively. Furthermore, testicular tissues were processed for histological evaluation and TUNEL staining.Key findingsExpressions of KIR6.1 protein and mRNA were more than 10-fold of those of KIR6.2 protein and mRNA in the testis. IR significantly increased the expressions of KIR6.1 protein and mRNA as well as KIR6.2 mRNA, caspase-3, and TUNEL index in the testis compared to the control. PARP expressions were significantly lower in the IR group than those of the control. Histologically, severe acute germ cell damage was observed in the IR testis. Treatment with cromakalim ameliorated these parameters compared to the non-treated IR group. There were no significant differences on Fas, FasL and protein level of KIR6.2 expressions between any of the groups.SignificanceTreatment with cromakalim has a protective effect against IR-induced testicular damage via activating KATP channels. This is the first study to give evidence for the advantageous effect of cromakalim in the germ cell-specific apoptosis induced by testicular IR. 相似文献
954.
Afendi FM Okada T Yamazaki M Hirai-Morita A Nakamura Y Nakamura K Ikeda S Takahashi H Altaf-Ul-Amin M Darusman LK Saito K Kanaya S 《Plant & cell physiology》2012,53(2):e1
A database (DB) describing the relationships between species and their metabolites would be useful for metabolomics research, because it targets systematic analysis of enormous numbers of organic compounds with known or unknown structures in metabolomics. We constructed an extensive species-metabolite DB for plants, the KNApSAcK Core DB, which contains 101,500 species-metabolite relationships encompassing 20,741 species and 50,048 metabolites. We also developed a search engine within the KNApSAcK Core DB for use in metabolomics research, making it possible to search for metabolites based on an accurate mass, molecular formula, metabolite name or mass spectra in several ionization modes. We also have developed databases for retrieving metabolites related to plants used for a range of purposes. In our multifaceted plant usage DB, medicinal/edible plants are related to the geographic zones (GZs) where the plants are used, their biological activities, and formulae of Japanese and Indonesian traditional medicines (Kampo and Jamu, respectively). These data are connected to the species-metabolites relationship DB within the KNApSAcK Core DB, keyed via the species names. All databases can be accessed via the website http://kanaya.naist.jp/KNApSAcK_Family/. KNApSAcK WorldMap DB comprises 41,548 GZ-plant pair entries, including 222 GZs and 15,240 medicinal/edible plants. The KAMPO DB consists of 336 formulae encompassing 278 medicinal plants; the JAMU DB consists of 5,310 formulae encompassing 550 medicinal plants. The Biological Activity DB consists of 2,418 biological activities and 33,706 pairwise relationships between medicinal plants and their biological activities. Current statistics of the binary relationships between individual databases were characterized by the degree distribution analysis, leading to a prediction of at least 1,060,000 metabolites within all plants. In the future, the study of metabolomics will need to take this huge number of metabolites into consideration. 相似文献
955.
956.
957.
958.
Ecotropic viral integration site-1 (EVI1) is one of the candidate oncogenes for human acute myeloid leukemia (AML) with chromosomal alterations at 3q26. High EVI1 expression (EVI1(high)) is a risk factor for AML with poor outcome. Using DNA microarray analysis, we previously identified that integrin α6 (ITGA6) was upregulated over 10-fold in EVI1(high) leukemia cells. In this study, we determined whether the increased expression of ITGA6 is associated with drug-resistance and increased cell adhesion, resulting in poor prognosis. To this end, we first confirmed the expression pattern of a series of integrin genes using semi-quantitative PCR and fluorescence-activated cell sorter (FACS) analysis and determined the cell adhesion ability in EVI1(high) leukemia cells. We found that the adhesion ability of EVI1(high) leukemia cells to laminin increased with the increased expression of ITGA6 and integrin β4 (ITGB4). The introduction of small-hairpin RNA against EVI1 (shEVI1) into EVI1(high) leukemia cells reduced the cell adhesion ability and downregulated the expression of ITGA6 and ITGB4. In addition, the overexpression of EVI1 in EVI1(low) leukemia cells enhanced their cell adhesion ability and increased the expression of ITGA6 and ITGB4. In a subsequent experiment, the introduction of shRNA against ITGA6 or ITGB4 into EVI1(high) AML cells downregulated their cell adhesion ability; however, the EVI1(high) AML cells transfected with shRNA against ITGA6 could not be maintained in culture. Moreover, treating EVI1(high) leukemia cells with neutralizing antibodies against ITGA6 or ITGB4 resulted in an enhanced responsiveness to anti-cancer drugs and a reduction of their cell adhesion ability. The expression of ITGA6 is significantly elevated in cells from relapsed and EVI1(high) AML cases; therefore, ITGA6 might represent an important therapeutic target for both refractory and EVI1(high) AML. 相似文献
959.
Activation-induced cytidine deminase (Aid), a unique enzyme that deaminates cytosine in DNA, shuttles between the nucleus and the cytoplasm. A recent study proposed a novel function of Aid in active DNA demethylation via deamination of 5-hydroxymethylcytosine, which is converted from 5-methylcytosine by the Ten-eleven translocation (Tet) family of enzymes. In this study, we examined the effect of simultaneous expression of Aid and Tet family proteins on the subcellular localization of each protein. We found that overexpressed Aid is mainly localized in the cytoplasm, whereas Tet1 and Tet2 are localized in the nucleus, and Tet3 is localized in both the cytoplasm and the nucleus. However, nuclear Tet proteins were gradually translocated to the cytoplasm when co-expressed with Aid. We also show that Aid-mediated translocation of Tet proteins is associated with Aid shuttling. Here we propose a possible role for Aid as a regulator of the subcellular localization of Tet family proteins. 相似文献
960.
The neural representation of motion aftereffects induced by various visual flows (translational, rotational, motion-in-depth,
and translational transparent flows) was studied under the hypothesis that the imbalances in discharge activities would occur
in favor in the direction opposite to the adapting stimulation in the monkey MST cells (cells in the medial superior temporal
area) which can discriminate the mode (i.e., translational, rotational, or motion-in-depth) of the given flow. In single-unit
recording experiments conducted on anaesthetized monkeys, we found that the rate of spontaneous discharge and the sensitivity
to a test stimulus moving in the preferred direction decreased after receiving an adapting stimulation moving in the preferred
direction, whereas they increased after receiving an adapting stimulation moving in the null direction. To consistently explain
the bidirectional perception of a transparent visual flow and its unidirectional motion aftereffect by the same hypothesis,
we need to assume the existence of two subtypes of MST D cells which show directionally selective responses to a translational
flow: component cells and integration cells. Our physiological investigation revealed that the MST D cells could be divided
into two types: one responded to a transparent flow by two peaks at the instances when the direction of one of the component
flow matched the preferred direction of the cell, and the other responded by a single peak at the instance when the direction
of the integrated motion matched the preferred direction. In psychophysical experiments on human subjects, we found evidence
for the existence of component and integration representations in the human brain. To explain the different motion perceptions,
i.e., two transparent flows during presentation of the flows and a single flow in the opposite direction to the integrated
flows after stopping the flow stimuli, we suggest that the pattern-discrimination system can select the motion representation
that is consistent with the perception of the pattern from two motion representations. We discuss the computational aspects
related to the integration of component motion fields. 相似文献