全文获取类型
收费全文 | 5466篇 |
免费 | 572篇 |
国内免费 | 1篇 |
专业分类
6039篇 |
出版年
2023年 | 23篇 |
2022年 | 63篇 |
2021年 | 120篇 |
2020年 | 81篇 |
2019年 | 125篇 |
2018年 | 150篇 |
2017年 | 124篇 |
2016年 | 186篇 |
2015年 | 264篇 |
2014年 | 292篇 |
2013年 | 323篇 |
2012年 | 422篇 |
2011年 | 356篇 |
2010年 | 240篇 |
2009年 | 196篇 |
2008年 | 276篇 |
2007年 | 231篇 |
2006年 | 228篇 |
2005年 | 210篇 |
2004年 | 190篇 |
2003年 | 199篇 |
2002年 | 180篇 |
2001年 | 133篇 |
2000年 | 133篇 |
1999年 | 113篇 |
1998年 | 55篇 |
1997年 | 52篇 |
1996年 | 57篇 |
1995年 | 47篇 |
1994年 | 52篇 |
1993年 | 46篇 |
1992年 | 80篇 |
1991年 | 71篇 |
1990年 | 76篇 |
1989年 | 59篇 |
1988年 | 59篇 |
1987年 | 53篇 |
1986年 | 38篇 |
1985年 | 43篇 |
1984年 | 28篇 |
1983年 | 38篇 |
1982年 | 39篇 |
1981年 | 33篇 |
1980年 | 20篇 |
1979年 | 31篇 |
1977年 | 26篇 |
1975年 | 19篇 |
1974年 | 20篇 |
1973年 | 18篇 |
1968年 | 17篇 |
排序方式: 共有6039条查询结果,搜索用时 15 毫秒
101.
102.
103.
Xabier Rodríguez‐Martínez Semih Sevim Xiaofeng Xu Carlos Franco Paula Pamies‐Puig Laura Crcoles‐Guija Romen Rodriguez‐Trujillo Francisco Javier del Campo David Rodriguez San Miguel Andrew J. deMello Salvador Pan David B. Amabilino Olle Ingans Josep Puigmartí‐Luis Mariano Campoy‐Quiles 《Liver Transplantation》2020,10(33)
Microfluidic technologies are highly adept at generating controllable compositional gradients in fluids, a feature that has accelerated the understanding of the importance of chemical gradients in biological processes. That said, the development of versatile methods to generate controllable compositional gradients in the solid‐state has been far more elusive. The ability to produce such gradients would provide access to extensive compositional libraries, thus enabling the high‐throughput exploration of the parametric landscape of functional solids and devices in a resource‐, time‐, and cost‐efficient manner. Herein, the synergic integration of microfluidic technologies is reported with blade coating to enable the controlled formation of compositional lateral gradients in solution. Subsequently, the transformation of liquid‐based compositional gradients into solid‐state thin films using this method is demonstrated. To demonstrate efficacy of the approach, microfluidic‐assisted blade coating is used to optimize blending ratios in organic solar cells. Importantly, this novel technology can be easily extended to other solution processable systems that require the formation of solid‐state compositional lateral gradients. 相似文献
104.
Nader Morshed William T Ralvenius Alexi Nott L Ashley Watson Felicia H Rodriguez Leyla A Akay Brian A Joughin PingChieh Pao Jay Penney Lauren LaRocque Diego Mastroeni LiHuei Tsai Forest M White 《Molecular systems biology》2020,16(12)
Alzheimer’s disease (AD) is characterized by the appearance of amyloid‐β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK‐p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec‐F which was upregulated on a subset of reactive microglia. The human paralog Siglec‐8 was also upregulated on microglia in AD. Siglec‐F and Siglec‐8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV‐2 cell line and human stem cell‐derived microglia models. Siglec‐F overexpression activates an endocytic and pyroptotic inflammatory response in BV‐2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine‐based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV‐2 cells. Collectively, our results point to an important role for mouse Siglec‐F and human Siglec‐8 in regulating microglial activation during neurodegeneration. 相似文献
105.
Ailec Ho‐Plagaro Concepcin Santiago‐Fernandez Cristina Rodríguez‐Díaz Carlos Lopez‐Gmez Sara Garcia‐Serrano Francisca Rodríguez‐Pacheco Sergio Valdes Alberto Rodríguez‐Caete Guillermo Alcaín‐Martínez Natalia Ruiz‐Santana Luis Vzquez‐Pedreo Eduardo García‐Fuentes 《Obesity (Silver Spring, Md.)》2020,28(9):1708-1717
106.
Blanca Domenech‐Ximenos Victor Cuba Pepus Daunis‐i‐Estadella Santiago Thi‐Henestrosa Francisco Jaldo Carles Biarnes Xavier Molina Gemma Xifra Wifredo Ricart Anton Bardera Imma Boada Marco Essig Salvador Pedraza Massimo Federici Jos Manuel Fernndez‐Real Josep Puig 《Obesity (Silver Spring, Md.)》2020,28(9):1663-1670
107.
Stefanie J. Müller‐Schüssele Ren Wang Desire D. Gütle Jill Romer Marta Rodriguez‐Franco Martin Scholz Felix Buchert Volker M. Lüth Stanislav Kopriva Peter Drmann Markus Schwarzlnder Ralf Reski Michael Hippler Andreas J. Meyer 《The Plant journal : for cell and molecular biology》2020,103(3):1140-1154
Thiol‐based redox‐regulation is vital for coordinating chloroplast functions depending on illumination and has been throroughly investigated for thioredoxin‐dependent processes. In parallel, glutathione reductase (GR) maintains a highly reduced glutathione pool, enabling glutathione‐mediated redox buffering. Yet, how the redox cascades of the thioredoxin and glutathione redox machineries integrate metabolic regulation and detoxification of reactive oxygen species remains largely unresolved because null mutants of plastid/mitochondrial GR are embryo‐lethal in Arabidopsis thaliana. To investigate whether maintaining a highly reducing stromal glutathione redox potential (EGSH) via GR is necessary for functional photosynthesis and plant growth, we created knockout lines of the homologous enzyme in the model moss Physcomitrella patens. In these viable mutant lines, we found decreasing photosynthetic performance and plant growth with increasing light intensities, whereas ascorbate and zeaxanthin/antheraxanthin levels were elevated. By in vivo monitoring stromal EGSH dynamics, we show that stromal EGSH is highly reducing in wild‐type and clearly responsive to light, whereas an absence of GR leads to a partial glutathione oxidation, which is not rescued by light. By metabolic labelling, we reveal changing protein abundances in the GR knockout plants, pinpointing the adjustment of chloroplast proteostasis and the induction of plastid protein repair and degradation machineries. Our results indicate that the plastid thioredoxin system is not a functional backup for the plastid glutathione redox systems, whereas GR plays a critical role in maintaining efficient photosynthesis. 相似文献
108.
Jing Zhang Dan Wu Yongxing He Lanlan Li Shanhui Liu Jianzhong Lu Huiming Gui Yuhan Wang Yan Tao Hanzhang Wang Dharam Kaushik Ronald Rodriguez Zhiping Wang 《Biochemistry and Biophysics Reports》2020
Reactivation of the androgen receptor signaling pathway in the emasculated environment is the main reason for the occurrence of castration-resistant prostate cancer (CRPC). The immunophilin FKBP51, as a co-chaperone protein, together with Hsp90 help the correct folding of AR. Rapamycin is a known small-molecule inhibitor of FKBP51, but its effect on the FKBP51/AR signaling pathway is not clear. In this study, the interaction mechanism between FKBP51 and rapamycin was investigated using steady-state fluorescence quenching, X-ray crystallization, MTT assay, and qRT-PCR. Steady-state fluorescence quenching assay showed that rapamycin could interact with FKBP51. The crystal of the rapamycin-FKBP51 complex indicated that rapamycin occupies the hydrophobic binding pocket of FK1 domain which is vital for AR activity. The residues involving rapamycin binding are mainly hydrophobic and may overlap with the AR interaction site. Further assays showed that rapamycin could inhibit the androgen-dependent growth of human prostate cancer cells by down-regulating the expression levels of AR activated downstream genes. Taken together, our study demonstrates that rapamycin suppresses AR signaling pathway by interfering with the interaction between AR and FKBP51. The results of this study not only can provide useful information about the interaction mechanism between rapamycin and FKBP51, but also can provide new clues for the treatment of prostate cancer and castration-resistant prostate cancer. 相似文献
109.
Studies have found that mutant, misfolded superoxide dismutase [Cu–Zn] (SOD1) can convert wild type SOD1 (wtSOD1) in a prion-like fashion, and that misfolded wtSOD1 can be propagated by release and uptake of protein aggregates. In developing a prion-like mechanism for this propagation of SOD1 misfolding we have previously shown how enervation of the SOD1 electrostatic loop (ESL), caused by the formation of transient non-obligate SOD1 oligomers, can lead to an experimentally observed gain of interaction (GOI) that results in the formation of SOD1 amyloid-like filaments. It has also been shown that freedom of ESL motion is essential to catalytic function. This work investigates the possibility that restricting ESL mobility might not only compromise superoxide catalytic activity but also serve to promote the peroxidase activity of SOD1, thus implicating the formation of SOD1 oligomers in both protein misfolding and in protein oxidation. 相似文献
110.
Santiago Herrera-lvarez Elinor Karlsson Oliver A Ryder Kerstin Lindblad-Toh Andrew J Crawford 《Molecular biology and evolution》2021,38(5):1715
Gigantism results when one lineage within a clade evolves extremely large body size relative to its small-bodied ancestors, a common phenomenon in animals. Theory predicts that the evolution of giants should be constrained by two tradeoffs. First, because body size is negatively correlated with population size, purifying selection is expected to be less efficient in species of large body size, leading to increased mutational load. Second, gigantism is achieved through generating a higher number of cells along with higher rates of cell proliferation, thus increasing the likelihood of cancer. To explore the genetic basis of gigantism in rodents and uncover genomic signatures of gigantism-related tradeoffs, we assembled a draft genome of the capybara (Hydrochoerus hydrochaeris), the world’s largest living rodent. We found that the genome-wide ratio of nonsynonymous to synonymous mutations (ω) is elevated in the capybara relative to other rodents, likely caused by a generation-time effect and consistent with a nearly neutral model of molecular evolution. A genome-wide scan for adaptive protein evolution in the capybara highlighted several genes controlling postnatal bone growth regulation and musculoskeletal development, which are relevant to anatomical and developmental modifications for an increase in overall body size. Capybara-specific gene-family expansions included a putative novel anticancer adaptation that involves T-cell-mediated tumor suppression, offering a potential resolution to the increased cancer risk in this lineage. Our comparative genomic results uncovered the signature of an intragenomic conflict where the evolution of gigantism in the capybara involved selection on genes and pathways that are directly linked to cancer. 相似文献