全文获取类型
收费全文 | 7063篇 |
免费 | 340篇 |
国内免费 | 309篇 |
专业分类
7712篇 |
出版年
2024年 | 11篇 |
2023年 | 81篇 |
2022年 | 161篇 |
2021年 | 169篇 |
2020年 | 226篇 |
2019年 | 327篇 |
2018年 | 328篇 |
2017年 | 212篇 |
2016年 | 219篇 |
2015年 | 186篇 |
2014年 | 445篇 |
2013年 | 708篇 |
2012年 | 215篇 |
2011年 | 425篇 |
2010年 | 234篇 |
2009年 | 298篇 |
2008年 | 311篇 |
2007年 | 331篇 |
2006年 | 276篇 |
2005年 | 290篇 |
2004年 | 261篇 |
2003年 | 234篇 |
2002年 | 191篇 |
2001年 | 113篇 |
2000年 | 97篇 |
1999年 | 92篇 |
1998年 | 94篇 |
1997年 | 114篇 |
1996年 | 112篇 |
1995年 | 91篇 |
1994年 | 73篇 |
1993年 | 80篇 |
1992年 | 71篇 |
1991年 | 55篇 |
1990年 | 34篇 |
1989年 | 47篇 |
1988年 | 31篇 |
1987年 | 41篇 |
1986年 | 34篇 |
1985年 | 37篇 |
1984年 | 84篇 |
1983年 | 51篇 |
1982年 | 58篇 |
1981年 | 34篇 |
1980年 | 31篇 |
1979年 | 33篇 |
1978年 | 11篇 |
1977年 | 17篇 |
1976年 | 12篇 |
1974年 | 14篇 |
排序方式: 共有7712条查询结果,搜索用时 0 毫秒
1.
Internode length in Pisum. I. The effect of the Le/le gene difference on endogenous gibberellin-like substances 总被引:2,自引:0,他引:2
The allelopathic potential of the dry fruits of Washingtonia filifera (L. Linden) H. Wendl. was investigated. Leachates from fruits inhibited the germination of lettuce, wheat, red cabbage and cucumber seeds. The inhibitory effect was partly neutralized by kinetin (20 mg 1−1 ) and gibberellic acid (50 mg 1−1 ). The effect of kinetin was more pronounced at 25°C than at 20°C. Substances inhibiting germination were localized in the pericarp of the fruit and were resistant to high temperature. 相似文献
2.
Ahmed Hasbi Jocelyne Polastron Stéphane Allouche Laura Stanasila Dominique Massotte Philippe Jauzac 《Journal of neurochemistry》1998,70(5):2129-2138
Abstract: Phosphorylation of G protein-coupled receptors is considered an important step during their desensitization. In SK-N-BE cells, recently presented as a pertinent model for the studies of the human δ-opioid receptor, pretreatment with the opioid agonist etorphine increased time-dependently the rate of phosphorylation of a 51-kDa membrane protein. Immunological characterization of this protein with an antibody, raised against the amino-terminal region of the cloned human δ-opioid receptor, revealed that it corresponded to the δ-opioid receptor. During prolonged treatment with etorphine, phosphorylation increased as early as 15 min to reach a maximum within 1 h. Phosphorylation and desensitization of adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the resensitization, a result strongly suggesting that phosphorylation of the δ-opioid receptor plays a prominent role in its rapid desensitization. The increase in phosphorylation of the δ-opioid receptor, as well as its desensitization, was not affected by H7, an inhibitor of protein kinase A and protein kinase C, but was drastically reduced by heparin or Zn2+ , known to act as G protein-coupled receptor kinase (GRK) inhibitors. These results are the first to show, on endogenously expressed human δ-opioid receptor, that a close link exists between receptor phosphorylation and agonist-promoted desensitization and that desensitization involves a GRK. 相似文献
3.
Influence of ionic strength and pH on the interaction between high-affinity heparin and antithrombin
Birgitta Nordenman Ingemar Björk 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,672(3):227-238
Binding constants for the binding of high-affinity heparin to antithrombin at different ionic strengths were determined by fluorescence titrations and were also estimated from dissociation curves of the heparin-antithrombin complex. These curves were monitored by near-ultraviolet circular dichroism or fluorescence. The dependence of the binding constant on the activity of NaCl suggested that maximally 5–6 charged groups are directly involved in the interaction between the two macromolecules. Major pH-dependent changes of the interaction, as evident by changes of the spectroscopic properties of the complex between the molecules, were found to occur below pH 5.5 and above pH 8.5. The acid change, which was irreversible, was most likely caused by an irreversible conformational change of antithrombin. At alkaline pH, however, the gross conformation of antithrombin was stable up to pH 12, while the affinity of high-affinity heparin for antithrombin began to decrease markedly at pH 8.5. The dissociation curve, which was reversible, had a midpoint around pH 9.5. This is compatible with the loss of affinity being caused by either a local conformational change, by ionization of tyrosine or by titration of one or more amino groups. 相似文献
4.
《Bioorganic & medicinal chemistry》2016,24(4):886-893
In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid–carbazole hybrid compounds were designed and synthesized. Ellman’s assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9 μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture. 相似文献
5.
《Bioorganic & medicinal chemistry》2016,24(8):1919-1926
Although several p53–Mdm2-binding disruptors have been identified to date, few studies have been published on p53–Mdmx-interaction inhibitors. In the present study, we demonstrated that o-aminothiophenol derivatives with molecular weights of 200–300 selectively inhibited the p53–Mdmx interaction. S-2-Isobutyramidophenyl 2-methylpropanethioate (K-178) (1c) activated p53, up-regulated the expression of its downstream genes such as p21 and Mdm2, and preferentially inhibited the growth of cancer cells with wild-type p53 over those with mutant p53. Furthermore, we found that the S-isobutyryl-deprotected forms 1b and 3b of 1c and S-2-benzamidophenyl 2-methylpropanethioate (K-181) (3c) preferentially inhibited the p53–Mdmx interaction over the p53–Mdm2 interaction, respectively, by using a Flag-p53 and glutathione S-transferase (GST)-fused protein complex (Mdm2, Mdmx, DAPK1, or PPID). In addition, the interaction of p53 with Mdmx was lost by replacing a sulfur atom with an oxygen atom in 1b and 1c. These results suggest that sulfides such as 1b, 3b, 4b, and 5b interfere with the binding of p53–Mdmx, resulting in the dissociation of the two proteins. Furthermore, the results of oral administration experiments using xenografts in nude mice indicated that 1c reduced the volume of tumor masses to 49.0% and 36.6% that of the control at 100 mg/kg and 150 mg/kg, respectively, in 40 days. 相似文献
6.
Yao Chen Jie Zhu Jun Mo Hongyu Yang Xueyang Jiang Hongzhi Lin 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):290-302
Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer’s disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure–activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50?=?10.2?±?1.2, 16.5?±?1.7, and 15.3?±?1.8?nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD. 相似文献
7.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献
8.
《Bioscience, biotechnology, and biochemistry》2013,77(1):98-101
Two novel nematicidal cyclodepsipeptides, designated bursaphelocides A and B, were isolated from the culture filtrate of an imperfect fungus, strain D1084, belonging to Mycelia sterilia. Bursaphelocide A (1), containing 2-hydroxy-3-methylpentanoic acid, proline, isoleucine, N-methylalanine, N-methylvaline, and β-alanine in sequence, and bursaphelocide B (2), comprising 4-methylproline instead of proline in 1, are novel 2-hydroxy-3-methylpentanoic acid analogues of insecticidal destruxins. 相似文献
9.
Mengnan Wang Dongjie Li Mingyue Zhang Wenzhi Yang Yali Cui Shijie Li 《Animal genetics》2015,46(4):354-360
The CDKN1C gene encodes a cyclin‐dependent kinase inhibitor and is one of the key genes involved in the development of Beckwith–Wiedemann syndrome and cancer. In this study, using a direct sequencing approach based on a single nucleotide polymorphism (SNP) at genomic DNA and cDNA levels, we show that CDKN1C exhibits monoallelic expression in all seven studied organs (heart, liver, spleen, lung, kidney, muscle and subcutaneous fat) in cattle. To investigate how methylation regulates imprinting of CDKN1C in cattle, allele‐specific methylation patterns in two putative differential methylation regions (DMRs), the CDKN1C DMR and KvDMR1, were analyzed in three tissues (liver, spleen and lung) using bisulfite sequencing PCR. Our results show that in the CDKN1C DMR both parental alleles were unmethylated in all three analyzed tissues. In contrast, KvDMR1 was differentially methylated between the two parental alleles in the same tissues. Statistical analysis showed that there is a significant difference in the methylation level between the two parental alleles (P < 0.01), confirming that this region is the DMR of KvDMR1 and that it may be correlated with CDKN1C imprinting. 相似文献
10.