全文获取类型
收费全文 | 1195篇 |
免费 | 62篇 |
出版年
2022年 | 8篇 |
2021年 | 19篇 |
2020年 | 16篇 |
2019年 | 17篇 |
2018年 | 29篇 |
2017年 | 18篇 |
2016年 | 25篇 |
2015年 | 38篇 |
2014年 | 60篇 |
2013年 | 82篇 |
2012年 | 95篇 |
2011年 | 91篇 |
2010年 | 52篇 |
2009年 | 47篇 |
2008年 | 81篇 |
2007年 | 69篇 |
2006年 | 56篇 |
2005年 | 62篇 |
2004年 | 50篇 |
2003年 | 55篇 |
2002年 | 48篇 |
2001年 | 12篇 |
2000年 | 18篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 7篇 |
1992年 | 14篇 |
1991年 | 5篇 |
1990年 | 14篇 |
1989年 | 18篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 9篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1968年 | 3篇 |
1965年 | 2篇 |
1963年 | 3篇 |
1962年 | 2篇 |
排序方式: 共有1257条查询结果,搜索用时 734 毫秒
41.
Magali Moreau Timothy Westlake Giulio Zampogna George Popescu Miaoying Tian Christos Noutsos Sorina Popescu 《The Plant journal : for cell and molecular biology》2013,76(4):603-614
Salicylic acid (SA) is a small phenolic molecule with hormonal properties, and is an essential component of the immune response. SA exerts its functions by interacting with protein targets; however, the specific cellular components modulated by SA and critical for immune signal transduction are largely unknown. To uncover cellular activities targeted by SA, we probed Arabidopsis protein microarrays with a functional analog of SA. We demonstrate that thimet oligopeptidases (TOPs) constitute a class of SA‐binding enzymes. Biochemical evidence demonstrated that SA interacts with TOPs and inhibits their peptidase activities to various degrees both in vitro and in plant extracts. Functional characterization of mutants with altered TOP expression indicated that TOP1 and TOP2 mediate SA‐dependent signaling and are necessary for the immune response to avirulent pathogens. Our results support a model whereby TOP1 and TOP2 act in separate pathways to modulate SA‐mediated cellular processes. 相似文献
42.
Claudio Battilocchio Giovanna Poce Salvatore Alfonso Giulio Cesare Porretta Sara Consalvi Lidia Sautebin Simona Pace Antonietta Rossi Carla Ghelardini Lorenzo Di Cesare Mannelli Silvia Schenone Antonio Giordani Luigia Di Francesco Paola Patrignani Mariangela Biava 《Bioorganic & medicinal chemistry》2013,21(13):3695-3701
We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules. 相似文献
43.
Simone Fattorini Agnese Sciotti Patrizio Tratzi Andrea Di Giulio 《Journal of Zoological Systematics and Evolutionary Research》2013,51(4):279-286
The most pervasive macroecological patterns concern (1) the frequency distribution of range size, (2) the relationship between range size and species abundance and (3) the effect of body size on range size. We investigated these patterns at a regional scale using the tenebrionid beetles of Latium (Central Italy). For this, we calculated geographical range size (no. of 10‐km square cells), ecological tolerance (no. of phytoclimatic units) and abundance (no. of sampled individuals) using a large database containing 3561 georeferenced records for 84 native species. For each species, we also calculated body mass and its ‘phylogenetic diversity’ on the basis of cladistic relationships. Frequency distribution of range size followed a log‐normal distribution as found in many other animal groups. However, a log‐normal distribution accommodated well the frequency distribution of ecological tolerance, a so far unexplored issue. Range size was correlated with abundance and ecological tolerance, thus supporting the hypothesis that a positive correlation between distribution and abundance is a reflection of interspecific differences in ecological specialization. Larger species tended to have larger ranges and broader ecological tolerance. However, contrary to what known in most vertebrates, not only small‐sized, but also many medium‐to‐large‐sized species exhibited great variability in their range size, probably because tenebrionids are not so strictly influenced by body size constraints (e.g. home ranges) as vertebrates. Moreover, in contrast to other animals, tenebrionid body size does not influence species abundances, probably because these detritivorous animals are not strongly regulated by competition. Finally, contrary to the assumption that rare species should be mainly found among lineages that split from basal nodes, rarity of a tenebrionid species was not influenced by the phylogenetic position of its tribe. However, lineages that split from more basal nodes had lower variability in terms of species geographical distribution, ecological tolerance and abundance, which suggests that lineages that split from more basal nodes are not only morphologically conservative but also tend to have an ecological ‘inertia’. 相似文献
44.
Jiannong Li Keiryn Bennett Alexey Stukalov Bin Fang Guolin Zhang Takeshi Yoshida Isamu Okamoto Jae‐Young Kim Lanxi Song Yun Bai Xiaoning Qian Bhupendra Rawal Michael Schell Florian Grebien Georg Winter Uwe Rix Steven Eschrich Jacques Colinge John Koomen Giulio Superti‐Furga Eric B Haura 《Molecular systems biology》2013,9(1)
We hypothesized that elucidating the interactome of epidermal growth factor receptor (EGFR) forms that are mutated in lung cancer, via global analysis of protein–protein interactions, phosphorylation, and systematically perturbing the ensuing network nodes, should offer a new, more systems‐level perspective of the molecular etiology. Here, we describe an EGFR interactome of 263 proteins and offer a 14‐protein core network critical to the viability of multiple EGFR‐mutated lung cancer cells. Cells with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) had differential dependence of the core network proteins based on the underlying molecular mechanisms of resistance. Of the 14 proteins, 9 are shown to be specifically associated with survival of EGFR‐mutated lung cancer cell lines. This included EGFR, GRB2, MK12, SHC1, ARAF, CD11B, ARHG5, GLU2B, and CD11A. With the use of a drug network associated with the core network proteins, we identified two compounds, midostaurin and lestaurtinib, that could overcome drug resistance through direct EGFR inhibition when combined with erlotinib. Our results, enabled by interactome mapping, suggest new targets and combination therapies that could circumvent EGFR TKI resistance. 相似文献
45.
Aims
Obesity and type 2 diabetes are characterised by low-grade inflammation, metabolic endotoxaemia (i.e., increased plasma lipopolysaccharides [LPS] levels) and altered endocannabinoid (eCB)-system tone. The aim of this study was to decipher the specific role of eCB-system stimulation or metabolic endotoxaemia in the onset of glucose intolerance, metabolic inflammation and altered lipid metabolism.Methods
Mice were treated with either a cannabinoid (CB) receptor agonist (HU210) or low-dose LPS using subcutaneous mini-pumps for 6 weeks. After 3 weeks of the treatment under control (CT) diet, one-half of each group of mice were challenged with a high fat (HF) diet for the following 3-week period.Results
Under basal conditions (control diet), chronic CB receptor agonist treatment (i.e., 6 weeks) induced glucose intolerance, stimulated metabolic endotoxaemia, and increased macrophage infiltration (CD11c and F4/80 expression) in the muscles; this phenomenon was associated with an altered lipid metabolism (increased PGC-1α expression and decreased CPT-1b expression) in this tissue. Chronic LPS treatment tended to increase the body weight and fat mass, with minor effects on the other metabolic parameters. Challenging mice with an HF diet following pre-treatment with the CB agonist exacerbated the HF diet-induced glucose intolerance, the muscle macrophage infiltration and the muscle''s lipid content without affecting the body weight or the fat mass.Conclusion
Chronic CB receptor stimulation under basal conditions induces glucose intolerance, stimulates metabolic inflammation and alters lipid metabolism in the muscles. These effects worsen following the concomitant ingestion of an HF diet. Here, we highlight the central roles played by the eCB system and LPS in the pathophysiology of several hallmarks of obesity and type 2 diabetes. 相似文献46.
Antonella Muscella Carla Vetrugno Luca Giulio Cossa Giovanna Antonaci Francesco De Nuccio Sandra Angelica De Pascali Francesco Paolo Fanizzi Santo Marsigliante 《PloS one》2016,11(11)
Malignant pleural mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy. There is an urgent need for effective therapy inasmuch as resistance, intrinsic and acquired, to conventional therapies is common. Among Pt(II) antitumor drugs, [Pt(O,O′-acac)(γ-acac)(DMS)] (Ptac2S) has recently attracted considerable attention due to its strong in vitro and in vivo antiproliferative activity and reduced toxicity. The purpose of this study was to examine the efficacy of Ptac2S treatment in MPM. We employed the ZL55 human mesothelioma cell line in vitro and in a murine xenograft model in vivo, to test the antitumor activity of Ptac2S. Cytotoxicity assays and Western blottings of different apoptosis and survival proteins were thus performed. Ptac2S increases MPM cell death in vitro and in vivo compared with cisplatin. Ptac2S was more efficacious than cisplatin also in inducing apoptosis characterized by: (a) mitochondria depolarization, (b) increase of bax expression and its cytosol-to-mitochondria translocation and decrease of Bcl-2 expression, (c) activation of caspase-7 and -9. Ptac2S activated full-length PKC-δ and generated a PKC-δ fragment. Full-length PKC-δ translocated to the nucleus and membrane, whilst PKC-δ fragment concentrated to mitochondria. Ptac2S was also responsible for the PKC-ε activation that provoked phosphorylation of p38. Both PKC-δ and PKC-ε inhibition (by PKC–siRNA) reduced the apoptotic death of ZL55 cells. Altogether, our results confirm that Ptac2S is a promising therapeutic agent for malignant mesothelioma, providing a solid starting point for its validation as a suitable candidate for further pharmacological testing. 相似文献
47.
Increasing evidence suggests that an appropriate model for food webs, the network of feeding links in a community of species, should take into account the inherent variability of ecological interactions. Harnessing this variability, we will show that it is useful to interpret empirically observed food webs as realisations of a family of stochastic processes, namely random dot‐product graph models. These models provide an ideal extension of food‐web models beyond the limitations of current deterministic or partially probabilistic models. As an additional bene?t, our RDPG framework enables us to identify the pairwise distance structure given by species' functional food‐web traits: this allows for the natural emergence of ecologically meaningful species groups. Lastly, our results suggest the notion that the evolutionary signature in food webs is already detectable in their stochastic backbones, while the contribution of their ?ne wiring is arguable. Synthesis Food webs are influenced by many stochastic processes and are constantly evolving. Here, we treat observed food webs as realisations of random dot‐product graph models (RDPG), extending food‐web modelling beyond the limitations of current deterministic or partially probabilistic models. Our RDPG framework enables us to identify the pairwise‐distance structure given by species' functional food‐web traits, which in turn allows for the natural emergence of ecologically meaningful species groups. It also provides a way to measure the phylogenetic signal present in food webs, which we find is strongest in webs' low‐dimensional backbones. 相似文献
48.
49.
50.
Marina Allegrezza Silvia Montecchiari Cecilia Ottaviani Veronica Pelliccia Giulio Tesei 《Plant biosystems》2019,153(4):616-623
This study presents the results of a floristic vegetational study on Robinia pseudoacacia neoformation forests in the peri-Adriatic sector of central Italy. This has allowed the characterization of these coenoses at the ecological, biogeographic, syntaxonomic and landscape levels. These currently represent the southernmost syntaxa of the Robinietea class described for the Italian peninsula, and the first syntaxonomic contribution of this class in Europe for the Mediterranean biogeographical region. We propose here the new alliance Lauro nobilis–Robinion pseudoacaciae of the order Chelidonio–Robinietalia pseudoacaciae and class Robinietea, with two new associations: Melisso altissimae–Robinietum pseudoacaciae and Rubio peregrinae–Robinietum pseudoacaciae. The new alliance Lauro nobilis–Robinion pseudoacaciae (typus: Melisso altissimae–Robinietum pseudoacaciae) brings together neoformation forests and pre-forest dominated by R. pseudoacacia in those territories with a Mediterranean macroclimate of the peri-Adriatic sector of central Italy. The optimum is found for the alluvial plain and low-slope morphologies, on soils that are moist and rich in organic matter and in areas with anthropic disturbance. On the basis of comparisons with the European context, the alliance Bryonio–Robinion described for the temperate territories of northern Italy is here validated. 相似文献