全文获取类型
收费全文 | 1441篇 |
免费 | 91篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 17篇 |
2021年 | 40篇 |
2020年 | 32篇 |
2019年 | 29篇 |
2018年 | 42篇 |
2017年 | 48篇 |
2016年 | 28篇 |
2015年 | 65篇 |
2014年 | 77篇 |
2013年 | 114篇 |
2012年 | 119篇 |
2011年 | 110篇 |
2010年 | 72篇 |
2009年 | 65篇 |
2008年 | 94篇 |
2007年 | 81篇 |
2006年 | 89篇 |
2005年 | 73篇 |
2004年 | 70篇 |
2003年 | 62篇 |
2002年 | 53篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 8篇 |
1997年 | 10篇 |
1996年 | 6篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1970年 | 2篇 |
1968年 | 3篇 |
1967年 | 3篇 |
排序方式: 共有1533条查询结果,搜索用时 31 毫秒
41.
42.
Ludmila F.M.F. Cardozo Liliana M. Pedruzzi Peter Stenvinkel Milena B. Stockler-Pinto Julio B. Daleprane Maurilo Leite Jr. Denise Mafra 《Biochimie》2013
The nuclear factor E2-related factor 2 (Nrf2) plays an important role in cellular protection against cancer, renal, pulmonary, cardiovascular and neurodegenerative diseases where oxidative stress and inflammation are common conditions. The Nrf2 regulates the expression of detoxifying enzymes by recognizing the human Antioxidant Response Element (ARE) binding site and it can regulate antioxidant and anti-inflammatory cellular responses, playing an important protective role on the development of the diseases. Studies designed to investigate how effective Nrf2 activators or modulators are need to be initiated. Several recent studies have shown that nutritional compounds can modulate the activation of Nrf2–Keap1 system. This review aims to discuss some of the key nutritional compounds that promote the activation of Nrf2, which may have impact on the human health. 相似文献
43.
Crescents consisting of a single lipoprotein membrane with an external protein scaffold comprise the initial structural elements of poxvirus morphogenesis. Crescents enlarge to form spherical immature virions, which enclose viroplasm consisting of proteins destined to form the cores of mature virions. Previous studies suggest that the L2 protein participates in the recruitment of endoplasmic reticulum (ER)-derived membranes to form immature virions within assembly sites of cytoplasmic factories. Here we show that L2 interacts with the previously uncharacterized 42-amino-acid A30.5 protein. An open reading frame similar in size to the one encoding A30.5 is at the same genome location in representatives of all chordopoxvirus genera. A30.5 has a putative transmembrane domain and colocalized with markers of the endoplasmic reticulum and with L2. By constructing a complementing cell line expressing A30.5, we isolated a deletion mutant virus that exhibits a defect in morphogenesis in normal cells. Large electron-dense cytoplasmic inclusions and clusters of scaffold protein-coated membranes that resemble crescents and immature virions devoid of viroplasm were seen in place of normal structures. Crescent-shaped membranes were continuous with the endoplasmic reticulum membrane and oriented with the convex scaffold protein-coated side facing the lumen, while clusters of completed spherical immature-virion-like forms were trapped within the expanded lumen. Immature-virion-like structures were more abundant in infected RK-13 cells than in BS-C-1 or HeLa cells, in which cytoplasmic inclusions were decorated with scaffold protein-coated membrane arcs. We suggest that the outer surface of the poxvirus virion is derived from the luminal side of the ER membrane. 相似文献
44.
María Eugenia Sabatino Liliana del Valle Sosa Juan Pablo Petiti Jorge Humberto Mukdsi Iván Darío Mascanfroni Claudia Gabriela Pellizas Silvina Gutiérrez Alicia Inés Torres Ana Lucía De Paul 《Experimental cell research》2013
Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K-Akt and NF-κB signaling pathways. 相似文献
45.
Veronika Slancarova Jana Zdanska Bohuslav Janousek Martina Talianova Christian Zschach Jitka Zluvova Jiri Siroky Viera Kovacova Hana Blavet Jiri Danihelka Bengt Oxelman Alex Widmer Boris Vyskot 《Evolution; international journal of organic evolution》2013,67(12):3669-3677
The plant genus Silene has become a model for evolutionary studies of sex chromosomes and sex‐determining mechanisms. A recent study performed in Silene colpophylla showed that dioecy and the sex chromosomes in this species evolved independently from those in Silene latifolia, the most widely studied dioecious Silene species. The results of this study show that the sex‐determining system in Silene otites, a species related to S. colpophylla, is based on female heterogamety, a sex determination system that is unique among the Silene species studied to date. Our phylogenetic data support the placing of S. otites and S. colpophylla in the subsection Otites and the analysis of ancestral states suggests that the most recent common ancestor of S. otites and S. colpophylla was most probably dioecious. These observations imply that a switch from XX/XY sex determination to a ZZ/ZW system (or vice versa) occurred in the subsection Otites. This is the first report of two different types of heterogamety within one plant genus of this mostly nondioecious plant family. 相似文献
46.
Hiroki Takagi Akira Abe Kentaro Yoshida Shunichi Kosugi Satoshi Natsume Chikako Mitsuoka Aiko Uemura Hiroe Utsushi Muluneh Tamiru Shohei Takuno Hideki Innan Liliana M. Cano Sophien Kamoun Ryohei Terauchi 《The Plant journal : for cell and molecular biology》2013,74(1):174-183
The majority of agronomically important crop traits are quantitative, meaning that they are controlled by multiple genes each with a small effect (quantitative trait loci, QTLs). Mapping and isolation of QTLs is important for efficient crop breeding by marker‐assisted selection (MAS) and for a better understanding of the molecular mechanisms underlying the traits. However, since it requires the development and selection of DNA markers for linkage analysis, QTL analysis has been time‐consuming and labor‐intensive. Here we report the rapid identification of plant QTLs by whole‐genome resequencing of DNAs from two populations each composed of 20–50 individuals showing extreme opposite trait values for a given phenotype in a segregating progeny. We propose to name this approach QTL‐seq as applied to plant species. We applied QTL‐seq to rice recombinant inbred lines and F2 populations and successfully identified QTLs for important agronomic traits, such as partial resistance to the fungal rice blast disease and seedling vigor. Simulation study showed that QTL‐seq is able to detect QTLs over wide ranges of experimental variables, and the method can be generally applied in population genomics studies to rapidly identify genomic regions that underwent artificial or natural selective sweeps. 相似文献
47.
Valerio Scali Liliana Milani Marco Passamonti 《Journal of Zoological Systematics and Evolutionary Research》2013,51(3):213-226
Recently, the Iberian stick insect genus Pijnackeria has been erected by splitting Leptynia Pantel on the basis of several distinguishing features. In addition to Pijnackeria hispanica, the tetraploid all‐female type species, molecular, karyological and SEM investigations led to the recognition of four bisexual and one triploid unisexual new species. Bisexuals' karyotypes (2n = 37/38) differ for minute traits and the haploid set is repeated, with few differences, three or four times in the polyploids that appeared to be of hybrid origin. Diagnostic morphological traits were found among body size parameters, antennal articles, male cerci, ovipositor valve and egg chorionic features. All species commonly feed on the broom Sarothamnus scoparius, but habitat disturbance appeared to induce food plant shifts. Moreover, trends from bisexuality to unisexuality through spanandry, probably related to habitat disruption, have been witnessed. The diploid species (Pijnackeria lucianae, Pijnackeria barbarae, Pijnackeria lelongi and Pijnackeria originis) have small ranges, while the polyploid hybrids (Pijnackeria masettii and P. hispanica) spread through Spain and Southern France, featuring a clear geographic parthenogenesis scenario, by colonizing wide areas and likely displacing their ancestors, or even leading them to extinction. Cyclic climatic changes and natural or anthropic habitat fragmentation may have been also of relevance in shaping present‐day distribution. 相似文献
48.
Gergana Gacheva Liliana Gigova Natalia Ivanova Ivan Iliev Reneta Toshkova Elena Gardeva Vesselin Kussovski Hristo Najdenski 《Journal of applied phycology》2013,25(1):183-194
The cytotoxic, antibacterial, and antifungal activities of cyanobacterium Gloeocapsa sp. strain Gacheva 2007/R-06/1 were investigated and the possibility for an enhancement of these activities by changing the culture conditions evaluated. Fatty acids of this cyanobacterium were found to be active against Streptococcus pyogenes. Exopolysaccharides inhibited the growth of both Gram-positive and Gram-negative bacteria and the fungus Candida albicans. Both exopolysaccharides and fatty acid mixtures also significantly decreased the viability of human cervical carcinoma cells, HeLa. Greater biological activities were exhibited by Gloeocapsa sp., cultured at suboptimal temperatures (15–26°C) than at optimal and supraoptimal ones. In comparison with higher light intensity, the low-light cultivation stimulated the cytotoxicity of the fatty acids. In general, low temperatures decreased the growth of Gloeocapsa sp., but promoted its biological activity. Prolonged cultivation also had a beneficial impact on the bioactivity. Compared to 4 days, the 17-day cultivation resulted in fourfold higher antibacterial and antifungal activities of exopolysaccharides and more than twice increases in their cytotoxicity. The study revealed that this cyanobacterial isolate is a new source of natural products with potential for pharmacological and medical applications. 相似文献
49.
Martin Neumann Ebru Coskun Lars Fransecky Liliana H. Mochmann Isabelle Bartram Nasrin Farhadi Sartangi Sandra Heesch Nicola G?kbuget Stefan Schwartz Christian Brandts Cornelia Schlee Rainer Haas Ulrich Dührsen Martin Griesshammer Hartmut D?hner Gerhard Ehninger Thomas Burmeister Olga Blau Eckhard Thiel Dieter Hoelzer Wolf-Karsten Hofmann Claudia D. Baldus 《PloS one》2013,8(1)
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup. 相似文献