全文获取类型
收费全文 | 7243篇 |
免费 | 601篇 |
国内免费 | 7篇 |
专业分类
7851篇 |
出版年
2023年 | 38篇 |
2022年 | 111篇 |
2021年 | 180篇 |
2020年 | 85篇 |
2019年 | 129篇 |
2018年 | 183篇 |
2017年 | 135篇 |
2016年 | 269篇 |
2015年 | 386篇 |
2014年 | 408篇 |
2013年 | 503篇 |
2012年 | 620篇 |
2011年 | 574篇 |
2010年 | 368篇 |
2009年 | 335篇 |
2008年 | 403篇 |
2007年 | 435篇 |
2006年 | 381篇 |
2005年 | 386篇 |
2004年 | 339篇 |
2003年 | 318篇 |
2002年 | 312篇 |
2001年 | 64篇 |
2000年 | 45篇 |
1999年 | 65篇 |
1998年 | 81篇 |
1997年 | 67篇 |
1996年 | 39篇 |
1995年 | 38篇 |
1994年 | 36篇 |
1993年 | 38篇 |
1992年 | 46篇 |
1991年 | 31篇 |
1990年 | 29篇 |
1989年 | 20篇 |
1988年 | 20篇 |
1987年 | 22篇 |
1986年 | 16篇 |
1985年 | 31篇 |
1984年 | 25篇 |
1983年 | 18篇 |
1982年 | 18篇 |
1981年 | 11篇 |
1980年 | 27篇 |
1979年 | 12篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 8篇 |
1974年 | 15篇 |
1973年 | 9篇 |
排序方式: 共有7851条查询结果,搜索用时 0 毫秒
81.
Two new species are added to the rare pompilid genus Abernessia Arlé. Abernessia capixaba
sp. n. and A. giga
sp. n. are described and illustrated. This is the first record of the genus from the states of Espírito Santo and Minas Gerais, Brazil. The genus now contains four species. A brief discussion of generic characters, illustrations, and a key to the known species of Abernessia are provided. 相似文献
82.
Wietske Lambert Gudrun Rutsdottir Rasha Hussein Katja Bernfur Sven Kjellstr?m Cecilia Emanuelsson 《Cell stress & chaperones》2013,18(1):75-85
Small heat-shock protein chaperones are important players in the protein quality control system of the cell, because they can immediately respond to partially unfolded proteins, thereby protecting the cell from harmful aggregates. The small heat-shock proteins can form large polydisperse oligomers that are exceptionally dynamic, which is implicated in their function of protecting substrate proteins from aggregation. Yet the mechanism of substrate recognition remains poorly understood, and little is known about what parts of the small heat-shock proteins interact with substrates and what parts of a partially unfolded substrate protein interact with the small heat-shock proteins. The transient nature of the interactions that prevent substrate aggregation rationalize probing this interaction by crosslinking mass spectrometry. Here, we used a workflow with lysine-specific crosslinking and offline nano-liquid chromatography matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry to explore the interaction between the plant small heat-shock protein Hsp21 and a thermosensitive model substrate protein, malate dehydrogenase. The identified crosslinks point at an interaction between the disordered N-terminal region of Hsp21 and the C-terminal presumably unfolding part of the substrate protein. 相似文献
83.
Stefano Pavan Adalgisa Schiavulli Michela Appiano Cecilia Miacola Richard G. F. Visser Yuling Bai Concetta Lotti Luigi Ricciardi 《Molecular breeding : new strategies in plant improvement》2013,31(1):247-253
Powdery mildew is the most widespread disease of pea (Pisum sativum L.) and causes severe economic losses worldwide. Recessively inherited er1 powdery mildew resistance, successfully used for decades in pea breeding programs, has recently been shown to originate from the loss of function of the PsMLO1 gene. Five er1 alleles, each corresponding to a different PsMLO1 null mutation, have been characterized to date in pea germplasm. In order to aid er1 selection, we aimed to identify functional markers which target PsMLO1 polymorphisms directly responsible for the resistant phenotype. Highly informative cleaved amplified polymorphic sequence (CAPS), derived cleaved amplified polymorphic sequence (dCAPS), sequence tagged site (STS) and high-resolution melting (HRM) markers were developed which enable the selection of each of the five er1 alleles. Taken together, the results described here provide a powerful tool for breeders, overcoming limitations of previously reported er1-linked markers due to the occurrence of recombination with the resistance locus and/or the lack of polymorphism between parental genotypes. The HRM marker er1-5/HRM54 reported here, targeting a mutagenesis-induced er1 allele recently described by us, does not require manual processing after PCR amplification, and is therefore suitable for large-scale breeding programs based on high-throughput automated screening. 相似文献
84.
Hebe Saraví Cisneros Mónica B. Bertiller Analía L. Carrera Cecilia Larreguy 《Plant Ecology》2013,214(11):1335-1343
Desert shrubs often accumulate different types of phenolic compounds but what determines the amount and diversity of these compounds is an issue scarcely explored. The aim of this study was to assess differences in the amount and diversity of phenolic compounds in leaves among coexisting shrub species differing in rooting depth and leaf turnover. We hypothesized that the diversity and amount of phenolic compounds in leaves of desert shrubs are related to access to soil water through rooting depth, and to leaf turnover. The study was carried out in the Patagonian Monte of Argentina. We collected green leaves of six species representing the dominant shrub morphotypes (tall evergreen, tall deciduous, and medium evergreen shrubs) and assessed lignin concentration and groups of soluble phenols obtained by sequential extraction with ethyl ether, ethyl acetate, and amyl alcohol. We also assessed nitrogen concentration in leaves and leaf mass per unit area (LMA) as traits related to leaf lifespan. The diversity of phenolic compounds was higher in green leaves of tall shrubs with deep rooting depth than in those of medium evergreen shrubs with shallow rooting depth. Diversity of phenolic compounds in green leaves was negatively related to lignin concentration. Evergreen shrubs had higher amount of phenolic compounds in green leaves than deciduous ones and the total amount of phenolic compounds in green leaves was positively related to LMA. We concluded that access to soil water sources and leaf turnover were related to the amount and diversity of phenolic compounds in green leaves of desert shrub species and these results are consistent with those predicted by the resource availability theory for plants from resource-rich and resource-poor habitats. 相似文献
85.
86.
Cecilia Marini Barbara Salani Michela Massollo Adriana Amaro Alessia Isabella Esposito Anna Maria Orengo Selene Capitanio Laura Emionite Mattia Riondato Gianluca Bottoni Cinzia Massara Simona Boccardo Marina Fabbi Cristina Campi Silvia Ravera Giovanna Angelini Silvia Morbelli Michele Cilli Renzo Cordera Mauro Truini Davide Maggi Ulrich Pfeffer Gianmario Sambuceti 《Cell cycle (Georgetown, Tex.)》2013,12(22):3490-3499
Emerging evidence suggests that metformin, a widely used anti-diabetic drug, may be useful in the prevention and treatment of different cancers. In the present study, we demonstrate that metformin directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB-231). The inhibition is selective for these isoforms, as documented by experiments with purified HK I and II as well as with cell lysates. Measurements of 18F-fluoro-deoxyglycose uptake document that it is dose- and time-dependent and powerful enough to virtually abolish glucose consumption despite unchanged availability of membrane glucose transporters. The profound energetic imbalance activates phosphorylation and is subsequently followed by cell death. More importantly, the “in vivo” relevance of this effect is confirmed by studies of orthotopic xenografts of MDA-MB-231 cells in athymic (nu/nu) mice. Administration of high drug doses after tumor development caused an evident tumor necrosis in a time as short as 48 h. On the other hand, 1 mo metformin treatment markedly reduced cancer glucose consumption and growth. Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer. 相似文献
87.
Natalia Y. Boynak Federico Rojas Cecilia D’Alessio Salomé C. Vilchez Larrea Vanina Rodriguez Pablo D. Ghiringhelli María T. Téllez-I?ón 《PloS one》2013,8(11)
Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs). Activation of the cyclin B-cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/M transition and inhibits mitotic entry by phosphorylating the inhibitory tyrosine 15 on the cdc2 M-phase-inducing kinase. Wee1 degradation is essential for the exit from the G2 phase. In trypanosomatids, little is known about the genes that regulate cyclin B-cdc2 complexes at the G2/M transition of their cell cycle. Although canonical tyrosine kinases are absent in the genome of trypanosomatids, phosphorylation on protein tyrosine residues has been reported in Trypanosoma brucei. Here, we characterized a Wee1-like protein kinase gene from T. brucei. Expression of TbWee1 in a Schizosaccharomyces pombe strain null for Wee1 inhibited cell division and caused cell elongation. This demonstrates the lengthening of G2, which provided cells with extra time to grow before dividing. The Wee1-like protein kinase was expressed in the procyclic and bloodstream proliferative slender forms of T. brucei and the role of Wee1 in cell cycle progression was analyzed by generating RNA interference cell lines. In the procyclic form of T. brucei, the knock-down of TbWee1 expression by RNAi led to inhibition of parasite growth. Abnormal phenotypes showing an increase in the percentage of cells with 1N0K, 0N1K and 2N1K were observed in these RNAi cell lines. Using parasites with a synchronized cell cycle, we demonstrated that TbWee1 is linked to the G2/M phase. We also showed that TbWee1 is an essential gene necessary for proper cell cycle progression and parasite growth in T. brucei. Our results provide evidence for the existence of a functional Wee1 in T. brucei with a potential role in cell division at G2/M. 相似文献
88.
The renin-angiotensin system expressed in adipose tissue has been implicated in the modulation of adipocyte formation, glucose metabolism, triglyceride accumulation, lipolysis, and the onset of the adverse metabolic consequences of obesity. As we investigated angiotensin II signal transduction mechanisms in human preadipose cells, an interplay of extracellular-signal-regulated kinases 1 and 2 (ERK1,2) and Akt/PKB became evident. Angiotensin II caused attenuation of phosphorylated Akt (p-Akt), at serine 473; the p-Akt/Akt ratio decreased to 0.5±0.2-fold the control value without angiotensin II (p<0.001). Here we report that the reduction of phosphorylated Akt associates with ERK1,2 activities. In the absence of angiotensin II, inhibition of ERK1,2 activation with U0126 or PD98059 resulted in a 2.1±0.5 (p<0.001) and 1.4±0.2-fold (p<0.05) increase in the p-Akt/Akt ratio, respectively. In addition, partial knockdown of ERK1 protein expression by the short hairpin RNA technique also raised phosphorylated Akt in these cells (the p-Akt/Akt ratio was 1.5±0.1-fold the corresponding control; p<0.05). Furthermore, inhibition of ERK1,2 activation with U0126 prevented the reduction of p-Akt/Akt by angiotensin II. An analogous effect was found on the phosphorylation status of Akt downstream effectors, the forkhead box (Fox) proteins O1 and O4. Altogether, these results indicate that angiotensin II signaling in human preadipose cells involves an ERK1,2-dependent attenuation of Akt activity, whose impact on the biological functions under its regulation is not fully understood. 相似文献
89.
Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus are used traditionally in Kenya for treatment of microbial infections and cancer. Information on their use is available, but scientific data on their bioactivity, safety and mechanisms of action is still scanty. A study was conducted on the effect of organic extracts of these plants on both bacterial and fungal strains, and their mechanisms of action. Extracts were evaluated through the disc diffusion assay. Bacteria and yeast test strains were cultured on Mueller-Hinton agar and on Sabouraud dextrose agar for the filamentous fungi. A 0.5 McFarland standard suspension was prepared. Sterile paper discs 6 mm in diameter impregnated with 10 µl of the test extract (100 mg/ml) were aseptically placed onto the surface of the inoculated media. Chloramphenicol (30 µg) and fluconazole (25 µg) were used as standards. Discs impregnated with dissolution medium were used as controls. Activity of the extracts was expressed according to zone of inhibition diameter. MIC was determined at 0.78–100 mg/ml. Safety studies were carried using Cell Counting Kit 8 cell proliferation assay protocol. To evaluate extracts mechanisms of action, IEC-6 cells and RT-PCR technique was employed in vitro to evaluate Interleukin 7 cytokine. Investigated plants extracts have both bactericidal and fungicidal activity. W. ugandensis is cytotoxic at IC50<50 µg/ml with MIC values of less than 0.78 mg/ml. Prunus africana shuts down expression of IL 7 mRNA at 50 µg/ml. W. somnifera has the best antimicrobial (1.5625 mg/ml), immunopotentiation (2 times IL 7 mRNA expression) and safety level (IC50>200 µg/ml). Fractions from W. ugandensis and W. somnifera too demonstrated antimicrobial activity. Mechanisms of action can largely be attributed to cytotoxicity, Gene silencing and immunopotentiation. Use of medicinal plants in traditional medicine has been justified and possible mechanisms of action demonstrated. Studies to isolate and characterize the bioactive constituents continue. 相似文献
90.
Anna S. Dean Guillaume Fournié Abalo E. Kulo G. Aboudou Boukaya Esther Schelling Bassirou Bonfoh 《PloS one》2013,8(10)