全文获取类型
收费全文 | 273篇 |
免费 | 29篇 |
出版年
2023年 | 3篇 |
2022年 | 2篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 8篇 |
2015年 | 6篇 |
2014年 | 13篇 |
2013年 | 13篇 |
2012年 | 19篇 |
2011年 | 30篇 |
2010年 | 8篇 |
2009年 | 9篇 |
2008年 | 14篇 |
2007年 | 12篇 |
2006年 | 18篇 |
2005年 | 16篇 |
2004年 | 7篇 |
2003年 | 4篇 |
2002年 | 10篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1997年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1980年 | 2篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1968年 | 2篇 |
1962年 | 3篇 |
1956年 | 1篇 |
1942年 | 2篇 |
1940年 | 2篇 |
1939年 | 1篇 |
1937年 | 2篇 |
1936年 | 2篇 |
1935年 | 3篇 |
1932年 | 2篇 |
1931年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有302条查询结果,搜索用时 15 毫秒
81.
High-resolution analysis of Y-chromosomal polymorphisms reveals signatures of population movements from central Asia and West Asia into India 总被引:6,自引:0,他引:6
Linguistic evidence suggests that West Asia and Central Asia have been the two major geographical sources of genes in the
contemporary Indian gene pool. To test the nature and extent of similarities in the gene pools of these regions we have collected
DNA samples from four ethnic populations of northern India, and have screened these samples for a set of 18 Y-chromosome polymorphic
markers (12 unique event polymorphisms and six short tandem repeats). These data from Indian populations have been analysed
in conjunction with published data from several West Asian and Central Asian populations. Our analyses have revealed traces
of population movement from Central Asia and West Asia into India. Two haplogroups, HG-3 and HG-9, which are known to have
arisen in the Central Asian region, are found in reasonably high frequencies (41.7% and 14.3% respectively) in the study populations.
The ages estimated for these two haplogroups are less in the Indian populations than those estimated from data on Middle Eastern
populations. A neighbour-joining tree based on Y-haplogroup frequencies shows that the North Indians are genetically placed
between the West Asian and Central Asian populations. This is consistent with gene flow from West Asia and Central Asia into
India. 相似文献
82.
B. R. Nebel 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1935,7(5):132-136
Ohne ZusammenfassungEin Referat über das Gesamtgebiet ist vonOehlkers angekündigt; hier handelt es sich um einen Teilausschnitt. Mit Zustimmung des DirektorsU. P. Hedrick als Institutsarbeit Nr. 52 der Agricultural Experiment Station angenommen 10/22/34. 相似文献
83.
84.
A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration
下载免费PDF全文
![点击此处可从《Molecular systems biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Vasiliki Maria Rogkoti Franziska Baenke Vincent C de Boer Christian Frezza Almut Schulze Eytan Ruppin 《Molecular systems biology》2014,10(8)
Over the last decade, the field of cancer metabolism has mainly focused on studying the role of tumorigenic metabolic rewiring in supporting cancer proliferation. Here, we perform the first genome‐scale computational study of the metabolic underpinnings of cancer migration. We build genome‐scale metabolic models of the NCI‐60 cell lines that capture the Warburg effect (aerobic glycolysis) typically occurring in cancer cells. The extent of the Warburg effect in each of these cell line models is quantified by the ratio of glycolytic to oxidative ATP flux (AFR), which is found to be highly positively associated with cancer cell migration. We hence predicted that targeting genes that mitigate the Warburg effect by reducing the AFR may specifically inhibit cancer migration. By testing the anti‐migratory effects of silencing such 17 top predicted genes in four breast and lung cancer cell lines, we find that up to 13 of these novel predictions significantly attenuate cell migration either in all or one cell line only, while having almost no effect on cell proliferation. Furthermore, in accordance with the predictions, a significant reduction is observed in the ratio between experimentally measured ECAR and OCR levels following these perturbations. Inhibiting anti‐migratory targets is a promising future avenue in treating cancer since it may decrease cytotoxic‐related side effects that plague current anti‐proliferative treatments. Furthermore, it may reduce cytotoxic‐related clonal selection of more aggressive cancer cells and the likelihood of emerging resistance. 相似文献
85.
Marian Beekman Hélène Blanché Markus Perola Anti Hervonen Vladyslav Bezrukov Ewa Sikora Friederike Flachsbart Lene Christiansen Anton J. M. De Craen Tom B. L. Kirkwood Irene Maeve Rea Michel Poulain Jean‐Marie Robine Silvana Valensin Maria Antonietta Stazi Giuseppe Passarino Luca Deiana Efstathios S. Gonos Lavinia Paternoster Thorkild I. A. Sørensen Qihua Tan Quinta Helmer Erik B. van den Akker Joris Deelen Francesca Martella Heather J. Cordell Kristin L. Ayers James W. Vaupel Outi Törnwall Thomas E. Johnson Stefan Schreiber Mark Lathrop Axel Skytthe Rudi G. J. Westendorp Kaare Christensen Jutta Gampe Almut Nebel Jeanine J. Houwing‐Duistermaat Pieternella Eline Slagboom Claudio Franceschi the GEHA consortium 《Aging cell》2013,12(2):184-193
Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome‐wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12‐q22 (LOD = 2.95), chromosome 19p13.3‐p13.11 (LOD = 3.76), and chromosome 19q13.11‐q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed‐effect meta‐analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P‐value = 9.6 × 10?8). By combined modeling of linkage and association, we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11‐q13.32 with P‐value = 0.02 and P‐value = 1.0 × 10?5, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12‐q22, and 19p13.3‐p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity. 相似文献
86.
Recent progress in industrial biocatalysis 总被引:2,自引:0,他引:2
In recent years, several procedures have been reported for the development of biocatalytic processes. This review focuses on selected examples integrating biocatalysts into a variety of industrially interesting processes ranging from the manufacture of smaller, chiral speciality chemicals to the synthesis of more complex pharmaceutical intermediates. The use of rational protein design, multistep processes and de novo design of enzyme catalysts for the stereocontrolled preparation of important target structures is discussed. 相似文献
87.
Almut Koehler Judith SchlupfMartina Schneider Bianca KraftClaudia Winter Jubin Kashef 《Developmental biology》2013
Xenopus cadherin-11 (Xcadherin-11) is an exceptional cadherin family member, which is predominantly expressed in cranial neural crest cells (NCCs). Apart from mediating cell–cell adhesion it promotes cranial NCC migration by initiating filopodia and lamellipodia formation. Here, we demonstrate an unexpected function of Xcadherin-11 in NCC specification by interfering with canonical Wnt/β-catenin signaling. Loss-of-function experiments, using a specific antisense morpholino oligonucleotide against Xcadherin-11, display a nuclear β-catenin localization in cranial NCCs and a broader expression domain of the proto-oncogene cyclin D1 which proceeds c-myc up-regulation. Additionally, we observe an enhanced NCC proliferation and an expansion of specific NCC genes like AP2 and Sox10. Thereby, we could allocate NCC proliferation and specification to different gene functions. To clarify which domain in Xcadherin-11 is required for early NCC development we tested different deletion mutants for their rescue ability in Xcadherin-11 morphants. We identified the cytoplasmic tail, specifically the β-catenin binding domain, to be necessary for proper NCC development. We propose that Xcadherin-11 is necessary for controlled NCC proliferation and early NCC specification in tuning the expression of the canonical Wnt/β-catenin target genes cyclin D1 and c-myc by regulating the concentration of the nuclear pool of β-catenin. 相似文献
88.
The introduction of alien species leads to changes in species composition and therefore the trophic structure. The highly invasive freshwater mysid Limnomysis benedeni is established and abundant in Lake Constance since 2006. Our aim was to confirm the assumption that L. benedeni feds on small particles and to identify their food web position. We examined the feeding mode and food preference of adult L. benedeni collected from the field and from laboratory feeding experiments by analysing their stomach contents. Stable isotope analyses (SIA) confirm an omnivorous feeding of L. benedeni. In laboratory growth experiments, we determined the growth of juveniles by feeding juveniles with different natural food sources. Growth was supported by natural biofilm, dreissenid biodeposited material and an algal suspension. Stomach analyses showed clearly that L. benedeni fed on small particles of both benthic and pelagic origin and fed by both filtering and grazing. Absence of high numbers of animal structures in the stomachs and SIA supported the lack of predatory impact in the field, but the mysid probably affects the nutrient cycles in the littoral. L. benedeni seems to play an important role in the trophic relations in Lake Constance and all other water bodies they invaded. 相似文献
89.
Pete Smith Katherine Calvin Johnson Nkem Donovan Campbell Francesco Cherubini Giacomo Grassi Vladimir Korotkov Anh Le Hoang Shuaib Lwasa Pamela McElwee Ephraim Nkonya Nobuko Saigusa Jean‐Francois Soussana Miguel Angel Taboada Frances C. Manning Dorothy Nampanzira Cristina Arias‐Navarro Matteo Vizzarri Jo House Stephanie Roe Annette Cowie Mark Rounsevell Almut Arneth 《Global Change Biology》2020,26(3):1532-1575
There is a clear need for transformative change in the land management and food production sectors to address the global land challenges of climate change mitigation, climate change adaptation, combatting land degradation and desertification, and delivering food security (referred to hereafter as “land challenges”). We assess the potential for 40 practices to address these land challenges and find that: Nine options deliver medium to large benefits for all four land challenges. A further two options have no global estimates for adaptation, but have medium to large benefits for all other land challenges. Five options have large mitigation potential (>3 Gt CO2eq/year) without adverse impacts on the other land challenges. Five options have moderate mitigation potential, with no adverse impacts on the other land challenges. Sixteen practices have large adaptation potential (>25 million people benefit), without adverse side effects on other land challenges. Most practices can be applied without competing for available land. However, seven options could result in competition for land. A large number of practices do not require dedicated land, including several land management options, all value chain options, and all risk management options. Four options could greatly increase competition for land if applied at a large scale, though the impact is scale and context specific, highlighting the need for safeguards to ensure that expansion of land for mitigation does not impact natural systems and food security. A number of practices, such as increased food productivity, dietary change and reduced food loss and waste, can reduce demand for land conversion, thereby potentially freeing‐up land and creating opportunities for enhanced implementation of other practices, making them important components of portfolios of practices to address the combined land challenges. 相似文献
90.
Gitta Lasslop Stijn Hantson Sandy P. Harrison Dominique Bachelet Chantelle Burton Matthias Forkel Matthew Forrest Fang Li Joe R. Melton Chao Yue Sally Archibald Simon Scheiter Almut Arneth Thomas Hickler Stephen Sitch 《Global Change Biology》2020,26(9):5027-5041
In this study, we use simulations from seven global vegetation models to provide the first multi‐model estimate of fire impacts on global tree cover and the carbon cycle under current climate and anthropogenic land use conditions, averaged for the years 2001–2012. Fire globally reduces the tree covered area and vegetation carbon storage by 10%. Regionally, the effects are much stronger, up to 20% for certain latitudinal bands, and 17% in savanna regions. Global fire effects on total carbon storage and carbon turnover times are lower with the effect on gross primary productivity (GPP) close to 0. We find the strongest impacts of fire in savanna regions. Climatic conditions in regions with the highest burned area differ from regions with highest absolute fire impact, which are characterized by higher precipitation. Our estimates of fire‐induced vegetation change are lower than previous studies. We attribute these differences to different definitions of vegetation change and effects of anthropogenic land use, which were not considered in previous studies and decreases the impact of fire on tree cover. Accounting for fires significantly improves the spatial patterns of simulated tree cover, which demonstrates the need to represent fire in dynamic vegetation models. Based upon comparisons between models and observations, process understanding and representation in models, we assess a higher confidence in the fire impact on tree cover and vegetation carbon compared to GPP, total carbon storage and turnover times. We have higher confidence in the spatial patterns compared to the global totals of the simulated fire impact. As we used an ensemble of state‐of‐the‐art fire models, including effects of land use and the ensemble median or mean compares better to observational datasets than any individual model, we consider the here presented results to be the current best estimate of global fire effects on ecosystems. 相似文献