全文获取类型
收费全文 | 6161篇 |
免费 | 405篇 |
国内免费 | 429篇 |
出版年
2024年 | 8篇 |
2023年 | 57篇 |
2022年 | 171篇 |
2021年 | 311篇 |
2020年 | 193篇 |
2019年 | 252篇 |
2018年 | 232篇 |
2017年 | 188篇 |
2016年 | 254篇 |
2015年 | 384篇 |
2014年 | 445篇 |
2013年 | 471篇 |
2012年 | 543篇 |
2011年 | 518篇 |
2010年 | 341篇 |
2009年 | 279篇 |
2008年 | 331篇 |
2007年 | 289篇 |
2006年 | 259篇 |
2005年 | 227篇 |
2004年 | 191篇 |
2003年 | 149篇 |
2002年 | 131篇 |
2001年 | 98篇 |
2000年 | 80篇 |
1999年 | 88篇 |
1998年 | 43篇 |
1997年 | 58篇 |
1996年 | 58篇 |
1995年 | 45篇 |
1994年 | 33篇 |
1993年 | 35篇 |
1992年 | 48篇 |
1991年 | 42篇 |
1990年 | 28篇 |
1989年 | 21篇 |
1988年 | 12篇 |
1987年 | 25篇 |
1986年 | 16篇 |
1985年 | 15篇 |
1984年 | 1篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有6995条查询结果,搜索用时 484 毫秒
251.
Yi‐zhou Tan Dong‐dong Fei Xiao‐ning He Ji‐min Dai Rong‐chen Xu Xin‐yue Xu Jun‐jie Wu Bei Li 《Cell proliferation》2019,52(4)
L‐type voltage‐gated calcium ion channels (L‐VGCCs) have been demonstrated to be the mediator of several significant intracellular activities in excitable cells, such as neurons, chromaffin cells and myocytes. Recently, an increasing number of studies have investigated the function of L‐VGCCs in non‐excitable cells, particularly stem cells. However, there appear to be no systematic reviews of the relationship between L‐VGCCs and stem cells, and filling this gap is prescient considering the contribution of L‐VGCCs to the proliferation and differentiation of several types of stem cells. This review will discuss the possible involvement of L‐VGCCs in stem cells, mainly focusing on osteogenesis mediated by mesenchymal stem cells (MSCs) from different tissues and neurogenesis mediated by neural stem/progenitor cells (NSCs). Additionally, advanced applications that use these channels as the target for tissue engineering, which may offer the hope of tissue regeneration in the future, will also be explored. 相似文献
252.
253.
Yumin Dai Ashley N. Peralta Jessica E. Wynn Chringma Sherpa Hao Li Astha Verma Stuart F.J. Le Grice Webster L. Santos 《Bioorganic & medicinal chemistry》2019,27(8):1759-1765
Interaction of HIV-1 rev response element (RRE) RNA with its cognate protein, Rev, is critical for HIV-1 replication. Understanding the mode of interaction between RRE RNA and ligands at the binding site can facilitate RNA molecular recognition as well as provide a strategy for developing anti-HIV therapeutics. Our approach utilizes branched peptides as a scaffold for multivalent binding to RRE IIB (high affinity rev binding site) with incorporation of unnatural amino acids to increase affinity via non-canonical interactions with the RNA. Previous high throughput screening of a 46,656-member library revealed several hits that bound RRE IIB RNA in the sub-micromolar range. In particular, the lead compound, 4B3, displayed a Kd value of 410?nM and demonstrated selectivity towards RRE. A ribonuclease protection assay revealed that 4B3 binds to the stem-loop structure of RRE IIB RNA, which was confirmed by SHAPE analysis with 234 nt long NL4-3 RRE RNA. Our studies further indicated interaction of 4B3 with both primary and secondary Rev binding sites. 相似文献
254.
Xiaoman Zheng Zhengfeng Fu Chunyun Wang Shengbo Zhang Min Dai Enbo Cai Yan Zhao 《Bioorganic & medicinal chemistry》2019,27(18):4211-4218
ObjectiveTo study the changes of ginsenoside content in different proportion of Panax ginseng-Angelica sinensis (GA) co-decoction, and to explore the amelioration of hematopoietic function in mice after combined use of the two drugs. The active ingredient profiles in P. ginseng single decoction and co-decoction of GA were determined by high performance liquid chromatography (HPLC). The experimental pharmacology method was used to explore the effect of GA co-decoction on the hematopoietic function of chemotherapy mice.ResultsThe active ingredient profiles of the co-decoction of GA significantly changed compared with those of the single decoction. Compared with GA1:0 (single decoction of Panax ginseng), the routine ginsenosides of all proportions of GA decreased significantly, but the proportion of rare ginsenosides increased significantly. The changes of contents of rare ginsenosides of GA were basically consistent with the trends of effects on the myelosuppression induced by CY. Compared with the model group, GA significantly increased the number of bone marrow nucleated cells, thymus index, peripheral blood leukocytes and platelets, and significantly reduced the spleen index. Moreover, GA could promote G1 phase bone marrow cells to enter the cell cycle, increase the proportion of S phase cells and G2/M phase cells, and increase the cell proliferation index.ConclusionGA can ameliorate the hematopoietic function of mice after chemotherapy, and GA2:3, GA3:2 were the best, which may be due to the changes of the pharmacodynamic material basis of GA after compatibility. All these results implied that GA may be an ideal drug and food supplement for the treatment of toxic and side effects of chemotherapeutic drugs. 相似文献
255.
256.
In this review, we summarize the rational design and versatile application of organic/inorganic hybrid gene carriers as multifunctional delivery systems. Organic/inorganic nanohybrids with both organic and inorganic components in one nanoparticle have attracted intense attention because of their favorable properties. Particularly, nanohybrids comprising cationic polymers and inorganic nanoparticles are considered to be promising candidates as multifunctional gene delivery systems. In this review, we begin with an introduction of gene delivery and gene carriers to demonstrate the incentive for fabricating nanohybrids as multifunctional carriers. Next, the construction strategies and morphology effects of organic/inorganic hybrid gene carriers are summarized and discussed. Both sections provide valuable information for the design and synthesis of hybrid gene carriers with superior properties. Finally, an overview is provided of the application of nanohybrids as multifunctional gene carriers. Diverse therapies and versatile imaging‐guided therapies have been achieved via the rational design of nanohybrids. In addition to a simple combination of the functions of organic and inorganic components, the performances arising from the synergistic effects of both components are considered to be more intriguing. In summary, this review might offer guidance for the understanding of organic/inorganic nanohybrids as multifunctional gene delivery systems. 相似文献
257.
Jun-Jiao Li Lei Zhou Chun-Mei Yin Dan-Dan Zhang Steven J. Klosterman Bao-Li Wang Jian Song Dan Wang Xiao-Ping Hu Krishna V. Subbarao Jie-Yin Chen Xiao-Feng Dai 《Environmental microbiology》2019,21(12):4852-4874
Verticillium dahliae is a soil-borne fungus that causes vascular wilt on numerous plants worldwide. The fungus survives in the soil for up to 14 years by producing melanized microsclerotia. The protective function of melanin in abiotic stresses is well documented. Here, we found that the V. dahliae tetraspan transmembrane protein VdSho1, a homolog of the Saccharomyces cerevisiae Sho1, acts as an osmosensor, and is required for plant penetration and melanin biosynthesis. The deletion mutant ΔSho1 was incubated on a cellophane membrane substrate that mimics the plant epidermis, revealing that the penetration of ΔSho1 strain was reduced compared to the wild-type strain. Furthermore, VdSho1 regulates melanin biosynthesis by a signalling mechanism requiring a kinase-kinase signalling module of Vst50-Vst11-Vst7. Strains, ΔVst50, ΔVst7 and ΔVst11 also displayed defective penetration and melanin production like the ΔSho1 strain. Defects in penetration and melanin production in ΔSho1 were restored by overexpression of Vst50, suggesting that Vst50 lies downstream of VdSho1 in the regulatory pathway governing penetration and melanin biosynthesis. Data analyses revealed that the transmembrane portion of VdSho1 was essential for both membrane penetration and melanin production. This study demonstrates that Vst50-Vst11-Vst7 module regulates VdSho1-mediated plant penetration and melanin production in V. dahliae, contributing to virulence. 相似文献
258.
Ting-Gang Li Bao-Li Wang Chun-Mei Yin Dan-Dan Zhang Dan Wang Jian Song Lei Zhou Zhi-Qiang Kong Steven J. Klosterman Jun-Jiao Li Sabiu Adamu Ting-Li Liu Krishna V. Subbarao Jie-Yin Chen Xiao-Feng Dai 《Molecular Plant Pathology》2019,20(6):857-876
Improving genetic resistance is a preferred method to manage Verticillium wilt of cotton and other hosts. Identifying host resistance is difficult because of the dearth of resistance genes against this pathogen. Previously, a novel candidate gene involved in Verticillium wilt resistance was identified by a genome-wide association study using a panel of Gossypium hirsutum accessions. In this study, we cloned the candidate resistance gene from cotton that encodes a protein sharing homology with the TIR-NBS-LRR receptor-like defence protein DSC1 in Arabidopsis thaliana (hereafter named GhDSC1). GhDSC1 expressed at higher levels in response to Verticillium wilt and jasmonic acid (JA) treatment in resistant cotton cultivars as compared to susceptible cultivars and its product was localized to nucleus. The transfer of GhDSC1 to Arabidopsis conferred Verticillium resistance in an A. thaliana dsc1 mutant. This resistance response was associated with reactive oxygen species (ROS) accumulation and increased expression of JA-signalling-related genes. Furthermore, the expression of GhDSC1 in response to Verticillium wilt and JA signalling in A. thaliana displayed expression patterns similar to GhCAMTA3 in cotton under identical conditions, suggesting a coordinated DSC1 and CAMTA3 response in A. thaliana to Verticillium wilt. Analyses of GhDSC1 sequence polymorphism revealed a single nucleotide polymorphism (SNP) difference between resistant and susceptible cotton accessions, within the P-loop motif encoded by GhDSC1. This SNP difference causes ineffective activation of defence response in susceptible cultivars. These results demonstrated that GhDSC1 confers Verticillium resistance in the model plant system of A. thaliana, and therefore represents a suitable candidate for the genetic engineering of Verticillium wilt resistance in cotton. 相似文献
259.
260.
Hanshu Wang Guishuan Wang Yubing Dai Zhenhua Li Yu Zhu Fei Sun 《Molecular reproduction and development》2019,86(9):1199-1209
G kinase‐anchoring protein 1 (GKAP1) is a G kinase‐associated protein that is conserved in many eutherians and is mainly expressed in the testis, especially in spermatocytes and round spermatids. The function of GKAP1 in the testis is largely unknown. Here, we revealed that deletion of GKAP1 led to an increase in sperm production with swollen epididymis, and germ cell apoptosis was found to decrease in GKAP1 knock‐out mice. Further investigations showed that a deficiency of GKAP1 could partly change the cellular location of cGK‐Iα and increase the amount of active cAMP response element‐binding protein (CREB) in the nucleus. Therefore, the expression of a particular inhibitor of apoptosis proteins (IAPs) was upregulated because of the activation of CREB, and this increase in IAPs was associated with a decrease in the level of activated caspase‐3. These results suggest that a deficiency of GKAP1 in mouse testis could increase sperm production through a reduction of the spontaneous apoptosis of germ cells in the testis, possibly because of a change in the activity of the cGK‐Iα pathway. 相似文献