全文获取类型
收费全文 | 2697篇 |
免费 | 128篇 |
专业分类
2825篇 |
出版年
2024年 | 1篇 |
2023年 | 18篇 |
2022年 | 32篇 |
2021年 | 64篇 |
2020年 | 54篇 |
2019年 | 69篇 |
2018年 | 90篇 |
2017年 | 68篇 |
2016年 | 119篇 |
2015年 | 145篇 |
2014年 | 154篇 |
2013年 | 204篇 |
2012年 | 261篇 |
2011年 | 238篇 |
2010年 | 135篇 |
2009年 | 118篇 |
2008年 | 181篇 |
2007年 | 210篇 |
2006年 | 154篇 |
2005年 | 167篇 |
2004年 | 109篇 |
2003年 | 95篇 |
2002年 | 81篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 14篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 4篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有2825条查询结果,搜索用时 15 毫秒
31.
Agnieszka Marek Ryszard Korona 《Evolution; international journal of organic evolution》2013,67(11):3077-3086
Radical shifts to new natural and human made niches can make some functions unneeded and thus exposed to genetic degeneration. Here we ask not about highly specialized and rarely used functions but those relating to major life‐history traits, rate of growth, and resistance to prolonged starvation. We found that in yeast each of the two traits was visibly impaired by at least several hundred individual gene deletions. There were relatively few deletions affecting negatively both traits and likely none harming one but improving the other. Functional profiles of gene deletions affecting either growth or survival were strikingly different: the first related chiefly to synthesis of macromolecules whereas the second to maintenance and recycling of cellular structures. The observed pattern of gene indispensability corresponds to that of gene induction, providing a rather rare example of agreement between the results of deletion and expression studies. We conclude that transitions to new environments in which the ability to grow at possibly fastest rate or survive under very long starvation become practically unnecessary can result in rapid erosion of these vital functions because they are coded by many genes constituting large mutational targets and because restricted pleiotropy is unlikely to constrain this process. 相似文献
32.
33.
Łukasz Grewling Bogdan Jackowiak Małgorzata Nowak Agnieszka Uruska Matt Smith 《Grana》2013,52(4):280-292
Birch (Betula) pollen seasons were examined in relation to meteorological conditions in Poznań (1996–2010). Birch pollen grains were collected using a volumetric spore trap. An alternate biennial cycle of birch pollen season intensity was noticed in Poznań. The main factors influencing birch pollen season intensity were average daily minimum temperatures during the second fortnight of May and the month of June one year before pollination as well as the intensity of the pollen season of the previous year. Most of the pollen grains are recorded during the first week of the season; the number of pollen grains recorded at this time is positively correlated with mean maximum temperature and negatively correlated with daily rainfall. The significant effect of rainfall in reducing the season pollen index was noticed only during weak pollen seasons (season pollen index <?mean). In addition, mean daily maximum temperature during the first two weeks of the birch pollen season markedly influences its duration. No significant trends in duration and intensity of the pollen season were recorded, however, a slight tendency towards early pollination was observed (?0.4 days/year, p?=?0.310). 相似文献
34.
The prevalence of the diapause response of the freshwater crustacean Daphnia magna to chemical cues on fish predation was evaluated in 35 clones originating from 14 European water bodies—inhabited or not inhabited by fish. Clonal lineages of experimental animals were cultured for 4 weeks in the presence or absence of water to which an extract of faeces of crucian carps (Carassius carassius), that were fed with Daphnia, was added. The proportion of females producing diapausing forms during the experimental period was used as a measure of the diapause response. A positive diapause response to fish predation cues was observed in 43% of investigated clones that originated from 71% of the water bodies tested. This indicated that the diapause response to fish scent is a common phenomenon in Daphnia magna from various locations in Europe. Surprisingly, no signs of a stronger diapause reaction to the tested cues were found in Daphnia originating from water bodies inhabited by fish compared with those from fish-free habitats. 相似文献
35.
Barbara Zambelli Katarzyna Banaszak Anna Merloni Agnieszka Kiliszek Wojciech Rypniewski Stefano Ciurli 《Journal of biological inorganic chemistry》2013,18(8):1005-1017
Urease is a nickel-dependent enzyme that plays a critical role in the biogeochemical nitrogen cycle by catalyzing the hydrolysis of urea to ammonia and carbamate. This enzyme, initially synthesized in the apo form, needs to be activated by incorporation of two nickel ions into the active site, a process driven by the dimeric metallochaperone UreE. Previous studies reported that this protein can bind different metal ions in vitro, beside the cognate Ni(II). This study explores the metal selectivity and affinity of UreE from Sporosarcina pasteurii (Sp, formerly known as Bacillus pasteurii) for cognate [Ni(II)] and noncognate [Zn(II)] metal ions. In particular, the thermodynamic parameters of SpUreE Ni(II) and Zn(II) binding have been determined using isothermal titration calorimetry. These experiments show that two Ni(II) ions bind to the protein dimer with positive cooperativity. The high-affinity site involves the conserved solvent-exposed His100 and the C-terminal His145, whereas the low-affinity site comprises also the C-terminal His147. Zn(II) binding to the protein, occurring in the same protein regions and with similar affinity as compared to Ni(II), causes metal-driven dimerization of the protein dimer. The crystal structure of the protein obtained in the presence of equimolar amounts of both metal ions indicates that the high-affinity metal binding site binds Ni(II) preferentially over Zn(II). The ability of the protein to select Ni(II) over Zn(II) was confirmed by competition experiments in solution as well as by analysis of X-ray anomalous dispersion data. Overall, the thermodynamics and structural parameters that modulate the metal ion specificity of the different binding sites on the protein surface of SpUreE have been established. 相似文献
36.
Agnieszka Misiura Ying Z. Pigli Susan Boyle‐Vavra Robert S. Daum Martin R. Boocock Phoebe A. Rice 《Molecular microbiology》2013,88(6):1218-1229
Methicillin‐resistant Staphylococcus aureus (MRSA) emerged via acquisition of a mobile element, staphylococcal cassette chromosome mec (SCCmec). Integration and excision of SCCmec is mediated by an unusual site‐specific recombination system. Most variants of SCCmec encode two recombinases, CcrA and CcrB, that belong to the large serine family. Since CcrA and CcrB are always found together, we sought to address their specific roles. We show here that CcrA and CcrB can carry out both excisive and integrative recombination in Escherichia coli in the absence of any host‐specific or SCCmec‐encoded cofactors. CcrA and CcrB are promiscuous in their substrate choice: they act on many non‐canonical pairs of recombination sites in addition to the canonical ones, which may explain tandem insertions into the SCCmec attachment site. Moreover, CcrB is always required, but CcrA is only required if one of the four half‐sites is present. Recombinational activity correlates with DNA binding: CcrA recognizes only that half‐site, which overlaps a conserved coding frame on the host chromosome. Therefore, we propose that CcrA serves as a specificity factor that emerged through modular evolution to enable recognition of a bacterial recombination site that is not an inverted repeat. 相似文献
37.
María García-Fernández Panagiotis Karras Agnieszka Checinska Estela Cañón Guadalupe T. Calvo Gonzalo Gómez-López 《Autophagy》2016,12(10):1776-1790
Melanoma is a paradigm of aggressive tumors with a complex and heterogeneous genetic background. Still, melanoma cells frequently retain developmental traits that trace back to lineage specification programs. In particular, lysosome-associated vesicular trafficking is emerging as a melanoma-enriched lineage dependency. However, the contribution of other lysosomal functions such as autophagy to melanoma progression is unclear, particularly in the context of metastasis and resistance to targeted therapy. Here we mined a broad spectrum of cancers for a meta-analysis of mRNA expression, copy number variation and prognostic value of 13 core autophagy genes. This strategy identified heterozygous loss of ATG5 at chromosome band 6q21 as a distinctive feature of advanced melanomas. Importantly, partial ATG5 loss predicted poor overall patient survival in a manner not shared by other autophagy factors and not recapitulated in other tumor types. This prognostic relevance of ATG5 copy number was not evident for other 6q21 neighboring genes. Melanocyte-specific mouse models confirmed that heterozygous (but not homozygous) deletion of Atg5 enhanced melanoma metastasis and compromised the response to targeted therapy (exemplified by dabrafenib, a BRAF inhibitor in clinical use). Collectively, our results support ATG5 as a therapeutically relevant dose-dependent rheostat of melanoma progression. Moreover, these data have important translational implications in drug design, as partial blockade of autophagy genes may worsen (instead of counteracting) the malignant behavior of metastatic melanomas. 相似文献
38.
39.
Edyta Paradowska Agnieszka Jab?ońska Miros?awa Studzińska Katarzyna Skowrońska Patrycja Suski Ma?gorzata Wi?niewska-Ligier Teresa Wo?niakowska-G?sicka Dorota Nowakowska Zuzanna Gaj Jan Wilczyński Zbigniew J. Le?nikowski 《PloS one》2016,11(4)
Toll-like receptor 9 (TLR9) recognizes non-methylated viral CpG-containing DNA and serves as a pattern recognition receptor that signals the presence of human cytomegalovirus (HCMV). Here, we present the genotype distribution of single-nucleotide polymorphisms (SNPs) of the TLR9 gene in infants and the relationship between TLR9 polymorphisms and HCMV infection. Four polymorphisms (-1237T/C, rs5743836; -1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) in the TLR9 gene were genotyped in 72 infants with symptomatic HCMV infection and 70 healthy individuals. SNP genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Digested fragments were separated and identified by capillary electrophoresis. The HCMV DNA copy number was measured by a quantitative real-time PCR assay. We found an increased frequency of heterozygous genotypes TLR9 -1486T/C and 2848C/T in infants with HCMV infection compared with uninfected cases. Heterozygous variants of these two SNPs increased the risk of HCMV disease in children (P = 0.044 and P = 0.029, respectively). In infants with a mutation present in at least one allele of -1486T/C and 2848C/T SNPs, a trend towards increased risk of cytomegaly was confirmed after Bonferroni’s correction for multiple testing (Pc = 0.063). The rs352139 GG genotype showed a significantly reduced relative risk for HCMV infection (Pc = 0.006). In contrast, the -1237T/C SNP was not related to viral infection. We found no evidence for linkage disequilibrium with the four examined TLR9 SNPs. The findings suggest that the TLR9 -1486T/C and 2848C/T polymorphisms could be a genetic risk factor for the development of HCMV disease. 相似文献
40.
Jagoda Kicielińska Agnieszka Szczygie? Joanna Rossowska Natalia Anger Katarzyna Kempińska Marta ?witalska Marta Kaszowska Joanna Wietrzyk Janusz Boratyński El?bieta Pajtasz-Piasecka 《PloS one》2016,11(2)