全文获取类型
收费全文 | 14808篇 |
免费 | 1039篇 |
国内免费 | 5篇 |
专业分类
15852篇 |
出版年
2023年 | 99篇 |
2022年 | 111篇 |
2021年 | 226篇 |
2020年 | 178篇 |
2019年 | 190篇 |
2018年 | 350篇 |
2017年 | 302篇 |
2016年 | 407篇 |
2015年 | 657篇 |
2014年 | 674篇 |
2013年 | 931篇 |
2012年 | 1171篇 |
2011年 | 1159篇 |
2010年 | 688篇 |
2009年 | 552篇 |
2008年 | 933篇 |
2007年 | 924篇 |
2006年 | 813篇 |
2005年 | 813篇 |
2004年 | 750篇 |
2003年 | 678篇 |
2002年 | 584篇 |
2001年 | 275篇 |
2000年 | 209篇 |
1999年 | 184篇 |
1998年 | 112篇 |
1997年 | 101篇 |
1996年 | 87篇 |
1995年 | 83篇 |
1994年 | 65篇 |
1993年 | 65篇 |
1992年 | 97篇 |
1991年 | 76篇 |
1990年 | 83篇 |
1989年 | 68篇 |
1988年 | 61篇 |
1987年 | 54篇 |
1986年 | 51篇 |
1985年 | 69篇 |
1984年 | 64篇 |
1983年 | 49篇 |
1982年 | 56篇 |
1981年 | 63篇 |
1980年 | 39篇 |
1979年 | 72篇 |
1978年 | 70篇 |
1976年 | 48篇 |
1975年 | 41篇 |
1974年 | 50篇 |
1971年 | 44篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
261.
Micha?l Beaulieu Anne-Mathilde Thierry Yvon Le Maho Yan Ropert-Coudert André Ancel 《Journal of Ornithology》2009,150(3):637-643
We investigated alloparental interactions and conditions which could facilitate or prevent the expression of alloparental
behaviours in Adélie penguins (Pygoscelis adeliae), a long-lived seabird which nests in high-density colonies around Antarctica. Observation sessions were carried out during
the crèche stage on 48 identified pairs and 50 identified chicks in a 217-nest subcolony. As the season progressed, young
were fed less often by their own parents because these were increasingly absent from the breeding site and less responsive
to their offspring’s solicitations. As a consequence, young and particularly those with a low body mass, coming from a two-chick
brood, opted for gradually soliciting more from other adults to obtain food, preferentially those nesting in their direct
vicinity. Unsuccessful breeders represented a low and constant part of the adult population and were not specifically solicited
by unrelated young. Despite the increasing chick demand, only 4.1% (3 out of 73) of alloparental solicitations resulted in
feeding, which is negligible compared to parental feeding. To investigate factors that could trigger the appearance of alloparental
care, we carried out comparisons with king (Aptenodytes patagonicus) and emperor penguins (Aptenodytes forsteri) which represent the closest species for which data on alloparental behaviour were available. Our results show different
trends to those observed in these species and three factors may explain the low occurrence of alloparental behaviour in Adélie
penguins: (1) the low and constant proportion of unsuccessful breeders, (2) the absence of chick selectivity towards unsuccessful
breeders, and (3) the late period of chick accessibility for potential alloparents. 相似文献
262.
Hélène Pereira Jean-François Martin Charlotte Joly Jean-Louis Sébédio Estelle Pujos-Guillot 《Metabolomics : Official journal of the Metabolomic Society》2010,6(2):207-218
In order to study the effect of a diet on metabolites found in body fluids such as plasma, we have developed and validated
a UPLC/MS method. While methods using NMR have been well established to analyse different biological tissues, recent studies
have described robust untargeted UPLC-MS methods for plasma analysis. One major concern when profiling plasma is the presence
of an important quantity of proteins which have to be precipitated without any loss of metabolites prior to LC/MS analysis.
The utilization of untargeted approaches in nutritional metabolomics still suffers from the lack of identification of specific
biomarkers. We therefore suggest an alternative method still using a global approach but focusing at the same time on metabolites
previously described in human plasma in order to detect biomarkers of metabolic dysregulations. Thus, to fulfil our objectives,
analytical parameters were tested (i) the anticoagulant type for sample collection, (ii) the protein precipitation method
and (iii) UPLC/MS analytical conditions. Three protein precipitation methods and two anticoagulants were tested and compared.
The method utilizing blood collection on heparin and methanol precipitation was chosen for giving the most reproducible results
while keeping the complexity of the sample. Finally, a validation was proposed to evaluate the stability of this analytical
method applied to a large batch of samples for nutritional metabolomic studies. 相似文献
263.
Leppänen J Huuskonen J Savolainen J Nevalainen T Taipale H Vepsäläinen J Gynther J Järvinen T 《Bioorganic & medicinal chemistry letters》2000,10(17):1967-1969
Entacapone was reacted with phosphorous oxychloride in dry pyridine to yield a phosphate ester. The phosphate promoiety increased aqueous solubility of the parent drug by more than 1700- and 20-fold at pH 1.2 and 7.4, respectively. The phosphate ester provides adequate stability (t(1/2) = 2227 h; pH 7.4) towards chemical hydrolysis, and allowed for release of the parent drug via enzymatic hydrolysis in liver homogenate. 相似文献
264.
Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperature and cooling agents,
such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of environmental cold stress such
as cold allodynia in dorsal root ganglion (DRG) neuron; however, the underlying mechanisms of action are unclear. We tested
the effects of physiological heat (37°C), anthralic acid (ACA and 0.025 mM), 2-aminoethyl diphenylborinate (2-APB and 0.05)
on noxious cold (10°C) and menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of rats. DRG neurons
were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM8 currents were consistently induced by noxious
cold or menthol. TRPM8 channels current densities of the neurons were higher in cold and menthol groups than in control. When
the physiological heat is introduced by chamber TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca2+ gates were blocked by the ACA although menthol-induced TRPM8 currents were not blocked by ACA and 2-APB. In conclusion, the
results suggested that activation of TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although we observed
the protective role of heat, ACA and 2-APB through a TRPM8 channel in nociceptive cold-activated DRG neurons. Since cold allodynia
is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology
in DRG neurons. 相似文献
265.
266.
Spatial mismatch in morphological,ecological and phylogenetic diversity,in historical and contemporary European freshwater fish faunas 下载免费PDF全文
Lucie Kuczynski Jessica Côte Aurèle Toussaint Sébastien Brosse Laëtitia Buisson Gaël Grenouillet 《Ecography》2018,41(10):1665-1674
Biodiversity encompasses multiple facets, among which taxonomic, functional and phylogenetic aspects are the most often considered. Understanding how those diversity facets are distributed and what are their determinants has become a central concern in the current context of biodiversity crisis, but such multi‐faceted measures over large geographical areas are still pending. Here, we measured the congruence between the biogeographical patterns of freshwater fish morphological, ecological and phylogenetic diversity across Europe and identified the natural and anthropogenic drivers shaping those patterns. Based on freshwater fish occurrence records in 290 European river catchments, we computed richness and evenness for morphological, ecological and phylogenetic diversity using standardized effect sizes for each diversity index. We then used linear models including climatic, geo‐morphological, biotic and human‐related factors to determine the key drivers shaping freshwater fish biodiversity patterns across Europe. We found a weak spatial congruence between facets of diversity. Patterns of diversity were mainly driven by elevation range, climatic seasonality and species richness while other factors played a minor role. Finally, we found that non‐native species introductions significantly affected diversity patterns and influenced the effects of some environmental drivers. Morphological, ecological and phylogenetic diversity constitute complementary facets of fish diversity rather than surrogates, testifying that they deserve to be considered altogether to properly assess biodiversity. Although the same environmental and anthropogenic factors overall explained those diversity facets, their relative influence varied. In the current context of global change, non‐native species introductions may also lead to important reshuffling of assemblages resulting in profound changes of diversity patterns. 相似文献
267.
Thein vitro susceptibilities of propolis and antifungal drugs were determined against some yeasts isolated from patients with superficial mycoses. The agents tested included fluconazole, itraconazole, ketoconazole, terbinafine and propolis. MICs were determined by the broth microdilution technique following National Committee for Clinical Laboratory Standards document M27-P. For allCandida albicans isolates from the patients with superficial mycoses, ketoconazole presented higher (P<0.05) efficiency than that of the other antifungal agents tested. The geometric mean MIC values of antifungal drugs and propolis against the yeasts tested ranged from 0.087 to 12.69 μg/mL and 0.4–0.6 μg/mL, respectively. Propolis also showed an important antifungal activity against the yeasts tested, MIC ranges of the propolis were between 0.01–1.65 μg/mL. Based on these results, propolis requires further investigation as a potential agent for the treatment of superficial mycoses. 相似文献
268.
Gasim Omer Elkhalifa Abd-Elfarag Lukudu Emmanuel Arthur W. D. Edridge Stella van Beers Mohamed B. Sebit Michaël B. van Hensbroek Ente J. J. Rood 《PLoS neglected tropical diseases》2022,16(7)
BackgroundNodding syndrome (NS) is a progressive neurological disease that has been described in several sub-Saharan African counties, but South Sudan is considered the most affected. However, knowledge about the exact burden and the epidemiological risk factors of NS in South Sudan is lacking.ObjectiveTo determine the prevalence, distribution and epidemiological risk factors of NS in the Greater Mundri area, the epicenter of NS in South Sudan.MethodsA NS prevalence house-to-house survey was conducted in multiple villages between February 2018 and November 2019. Geographical distribution and clustering of NS cases was identified using spatial and binomial regression analysis. Epidemiological risk factors of NS were identified using univariate and multivariate models.ResultsOf the 22,411 persons surveyed in 92 villages, 607 (2.7%) persons with NS were identified, of which 114 (19%) were new-onset cases. The highest prevalence was found in Diko village with a prevalence of 13.7%. NS showed a significant spatial pattern with clustering of cases between adjacent households and along rivers. Risks factors for NS include all behaviors around rivers (drinking, cooking, handwashing and bathing) and exposure to poultry. On the other hand, ownership of mobile phone decreased the risk of NS. Many other factors, including prior ivermectin treatment and internal displacement were not associated with NS.ConclusionOur study demonstrates a very high burden of the NS disease in the Greater Mundri area, strengthens the association with rivers, and identified possible new clues for an underlying cause. 相似文献
269.
Aldo Spanjaard Ronak Shah Daniël de
Groot Olimpia Alessandra Buoninfante Ben Morris Cor Lieftink Colin Pritchard Lisa
M Zürcher Shirley Ormel Joyce J I Catsman Renske de
Korte-Grimmerink Bjrn Siteur Natalie Proost Terry Boadum Marieke van
de
Ven Ji-Ying Song Maaike Kreft Paul C M van
den
Berk Roderick
L Beijersbergen Heinz Jacobs 《Nucleic acids research》2022,50(13):7420
Crosslink repair depends on the Fanconi anemia pathway and translesion synthesis polymerases that replicate over unhooked crosslinks. Translesion synthesis is regulated via ubiquitination of PCNA, and independently via translesion synthesis polymerase REV1. The division of labor between PCNA-ubiquitination and REV1 in interstrand crosslink repair is unclear. Inhibition of either of these pathways has been proposed as a strategy to increase cytotoxicity of platinating agents in cancer treatment. Here, we defined the importance of PCNA-ubiquitination and REV1 for DNA in mammalian ICL repair. In mice, loss of PCNA-ubiquitination, but not REV1, resulted in germ cell defects and hypersensitivity to cisplatin. Loss of PCNA-ubiquitination, but not REV1 sensitized mammalian cancer cell lines to cisplatin. We identify polymerase Kappa as essential in tolerating DNA damage-induced lesions, in particular cisplatin lesions. Polk-deficient tumors were controlled by cisplatin treatment and it significantly delayed tumor outgrowth and increased overall survival of tumor bearing mice. Our results indicate that PCNA-ubiquitination and REV1 play distinct roles in DNA damage tolerance. Moreover, our results highlight POLK as a critical TLS polymerase in tolerating multiple genotoxic lesions, including cisplatin lesions. The relative frequent loss of Polk in cancers indicates an exploitable vulnerability for precision cancer medicine. 相似文献
270.
Paula Martínez Raúl Snchez-Vzquez Iole Ferrara-Romeo Rosa Serrano Juana M. Flores Maria A. Blasco 《PLoS genetics》2022,18(6)
The shelterin protein POT1 has been found mutated in many different familial and sporadic cancers, however, no mouse models to understand the pathobiology of these mutations have been developed so far. To address the molecular mechanisms underlying the tumorigenic effects of POT1 mutant proteins in humans, we have generated a mouse model for the human POT1R117C mutation found in Li-Fraumeni-Like families with cases of cardiac angiosarcoma by introducing this mutation in the Pot1a endogenous locus, knock-in for Pot1aR117C. We find here that both mouse embryonic fibroblasts (MEFs) and tissues from Pot1a+/ki mice show longer telomeres than wild-type controls. Longer telomeres in Pot1a+/ki MEFs are dependent on telomerase activity as they are not found in double mutant Pot1a+/ki Tert-/- telomerase-deficient MEFs. By using complementation assays we further show that POT1a pR117C exerts dominant-negative effects at telomeres. As in human Li-Fraumeni patients, heterozygous Pot1a+/ki mice spontaneously develop a high incidence of angiosarcomas, including cardiac angiosarcomas, and this is associated to the presence of abnormally long telomeres in endothelial cells as well as in the tumors. The Pot1a+/R117C mouse model constitutes a useful tool to understand human cancers initiated by POT1 mutations. 相似文献