全文获取类型
收费全文 | 41640篇 |
免费 | 16567篇 |
国内免费 | 1561篇 |
专业分类
59768篇 |
出版年
2024年 | 48篇 |
2023年 | 217篇 |
2022年 | 587篇 |
2021年 | 1084篇 |
2020年 | 2659篇 |
2019年 | 4287篇 |
2018年 | 4313篇 |
2017年 | 4515篇 |
2016年 | 4645篇 |
2015年 | 4944篇 |
2014年 | 4742篇 |
2013年 | 5227篇 |
2012年 | 3250篇 |
2011年 | 2885篇 |
2010年 | 3881篇 |
2009年 | 2547篇 |
2008年 | 1658篇 |
2007年 | 1099篇 |
2006年 | 982篇 |
2005年 | 945篇 |
2004年 | 937篇 |
2003年 | 778篇 |
2002年 | 694篇 |
2001年 | 625篇 |
2000年 | 494篇 |
1999年 | 408篇 |
1998年 | 151篇 |
1997年 | 102篇 |
1996年 | 96篇 |
1995年 | 92篇 |
1994年 | 83篇 |
1993年 | 65篇 |
1992年 | 108篇 |
1991年 | 91篇 |
1990年 | 71篇 |
1989年 | 62篇 |
1988年 | 47篇 |
1987年 | 31篇 |
1986年 | 35篇 |
1985年 | 33篇 |
1984年 | 13篇 |
1983年 | 21篇 |
1982年 | 16篇 |
1981年 | 13篇 |
1980年 | 23篇 |
1979年 | 23篇 |
1977年 | 19篇 |
1975年 | 14篇 |
1974年 | 17篇 |
1970年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 9 毫秒
161.
162.
Zeina Daher Ghislaine Recorbet Benoît Valot Frank Robert Thierry Balliau Sophie Potin Benoît Schoefs Eliane Dumas‐Gaudot 《Proteomics》2010,10(11):2123-2137
Despite the recognized importance of non‐photosynthetic plastids in a wide array of plant processes, the root plastid proteome of soil‐grown plants still remains to be explored. In this study, we used a protocol allowing the isolation of Medicago truncatula root plastids with sufficient protein recovery and purity for their subsequent in‐depth analysis by nanoscale capillary LC‐MS/MS. Besides providing the first picture of a root plastid proteome, the results obtained highlighted the identification of 266 protein candidates whose functional distribution mainly resembled that of wheat endosperm amyloplasts and tobacco proplastids together with displaying major differences to those reported for chloroplasts. Most of the identified proteins have a role in nucleic acid‐related processes (16%), carbohydrate (15%) and nitrogen/sulphur (12%) metabolisms together with stress response mechanisms (10%). It is noteworthy that BLAST searches performed against the proteins reported in different plastidomes allowed detecting 30 putative root plastid proteins for which homologues were previously unsuspected as plastid‐located, most of them displaying a common putative role in participating in the plant cell responses against abiotic and/or biotic stresses. Taken together, the data obtained provide new insights into the functioning of root plastids and reinforce the emerging idea for an important role of these organelles in sustaining plant defence reactions. 相似文献
163.
Ren Kong Ran-Ran Liu Xi-Ming Xu Da-Wei Zhang Xiao-Shuang Xu Hang Shi Shan Chang 《Proteins》2020,88(8):1100-1109
Integration of template-based modeling, global sampling and precise scoring is crucial for the development of molecular docking programs with improved accuracy. We combined template-based modeling and ab-initio docking protocol as hybrid docking strategy called CoDock for the docking and scoring experiments of the seventh CAPRI edition. For CAPRI rounds 38-45, we obtained acceptable or better models in the top 10 submissions for eight out of the 16 evaluated targets as predictors, nine out of the 16 targets as scorers. Especially, we submitted acceptable models for all of the evaluated protein-oligosaccharide targets. For the CASP13-CAPRI experiment (round 46), we obtained acceptable or better models in the top 5 submissions for 10 out of the 20 evaluated targets as predictors, 11 out of the 20 targets as scorers. The failed cases for our group were mainly the difficult targets and the protein-peptide systems in CAPRI and CASP13-CAPRI experiments. In summary, this CAPRI edition showed that our hybrid docking strategy can be efficiently adapted to the increasing variety of challenges in the field of molecular interactions. 相似文献
164.
Dai Sik Ko Junho Kang Hye Jin Heo Eun Kyoung Kim Kihun Kim Jin Mo Kang YunJae Jung Seung Eun Baek Yun Hak Kim 《International journal of biological sciences》2022,18(13):5154
Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (, GSE28829, GSE43292, and GSE100927), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro. Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 (PCK2) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2-KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis. GSE120521相似文献
165.
Tina B McKay Akhee Sarker‐Nag Desiree' Lyon John M Asara Dimitrios Karamichos 《Cell biochemistry and function》2015,33(5):341-350
Corneal scarring is the result of a disease, infection or injury. The resulting scars cause significant loss of vision or even blindness. To‐date, the most successful treatment is corneal transplantation, but it does not come without side effects. One of the corneal dystrophies that are correlated with corneal scarring is keratoconus (KC). The onset of the disease is still unknown; however, altered cellular metabolism has been linked to promoting the fibrotic phenotype and therefore scarring. We have previously shown that human keratoconus cells (HKCs) have altered metabolic activity when compared to normal human corneal fibroblasts (HCFs). In our current study, we present evidence that quercetin, a natural flavonoid, is a strong candidate for regulating metabolic activity of both HCFs and HKCs in vitro and therefore a potential therapeutic to target the altered cellular metabolism characteristic of HKCs. Targeted mass spectrometry‐based metabolomics was performed on HCFs and HKCs with and without quercetin treatment in order to identify variations in metabolite flux. Overall, our study reveals a novel therapeutic target OF Quercetin on corneal stromal cell metabolism in both healthy and diseased states. Clearly, further studies are necessary in order to dissect the mechanism of action of quercetin. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
166.
167.
Increased versican expression in breast tumors is predictive of relapse and has negative impact on survival rates. The C-terminal G3 domain of versican influences local and systemic tumor invasiveness in pre-clinical murine models. However, the mechanism(s) by which G3 influences breast tumor growth and metastasis is not well characterized. Here we evaluated the expression of versican in mouse mammary tumor cell lines observing that 4T1 cells expressed highest levels while 66c14 cells expressed low levels. We exogenously expressed a G3 construct in 66c14 cells and analyzed its effects on cell proliferation, migration, cell cycle progression, and EGFR signaling. Experiments in a syngeneic orthotopic animal model demonstrated that G3 promoted tumor growth and systemic metastasis in vivo. Activation of pERK correlated with high levels of G3 expression. In vitro, G3 enhanced breast cancer cell proliferation and migration by up-regulating EGFR signaling, and enhanced cell motility through chemotactic mechanisms to bone stromal cells, which was prevented by inhibitor AG 1478. G3 expressing cells demonstrated increased CDK2 and GSK-3β (S9P) expression, which were related to cell growth. The activity of G3 on mouse mammary tumor cell growth, migration and its effect on spontaneous metastasis to bone in an orthotopic model was modulated by up-regulating the EGFR-mediated signaling pathway. Taken together, EGFR-signaling appears to be an important pathway in versican G3-mediated breast cancer tumor invasiveness and metastasis. 相似文献
168.
The role of ungulates in nowadays temperate forests. A response to Fløjgaard et al. (DOI:10.1111/gcb.14029) 下载免费PDF全文
169.
Annelie Eklund Sarron Randall‐Demllo Sergey Shabala Nuri Guven Anthony L Cook Rajaraman D Eri 《Cell biochemistry and function》2013,31(7):603-611
Endoplasmic reticulum (ER) stress and oxidative stress have recently been linked to the pathogenesis of inflammatory bowel diseases. Under physiological conditions, intestinal epithelial cells are exposed to ER and oxidative stress affecting the cellular ionic homeostasis. However, these altered ion flux ‘signatures’ during these stress conditions are poorly characterized. We investigated the kinetics of K+, Ca2+ and H+ ion fluxes during ER and oxidative stress in a colonic epithelial cell line LS174T using a non‐invasive microelectrode ion flux estimation technique. ER and oxidative stress were induced by cell exposure to tunicamycin (TM) and copper ascorbate (CuAsc), respectively, from 1 to 24 h. Dramatic K+ efflux was observed following acute ER stress with peak K+ efflux being ?30·6 and ?138·7 nmolm?2 s?1 for 10 and 50 µg ml?1, respectively (p < 0·01). TM‐dependent Ca2+ uptake was more prolonged with peak values of 0·85 and 2·68 nmol m?2 s?1 for 10 and 50 µg ml?1 TM, respectively (p < 0·02). Ion homeostasis was also affected by the duration of ER stress. Increased duration of TM treatment from 0 to 18 h led to increases in both K+ efflux and Ca2+ uptake. While K+ changes were significantly higher at each time point tested, Ca2+ uptake was significantly higher only after prolonged treatment (18 h). CuAsc also led to an increased K+ efflux and Ca2+ uptake. Functional assays to investigate the effect of inhibiting K+ efflux with tetraethylammonium resulted in increased cell viability. We conclude that ER/oxidative stress in colonic epithelial cells cause dramatic K+, Ca2+ and H+ ion flux changes, which may predispose this lineage to poor stress recovery reminiscent of that seen in inflammatory bowel diseases. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
170.