全文获取类型
收费全文 | 11657篇 |
免费 | 1015篇 |
国内免费 | 6篇 |
出版年
2024年 | 11篇 |
2023年 | 85篇 |
2022年 | 189篇 |
2021年 | 367篇 |
2020年 | 230篇 |
2019年 | 323篇 |
2018年 | 324篇 |
2017年 | 297篇 |
2016年 | 472篇 |
2015年 | 767篇 |
2014年 | 883篇 |
2013年 | 925篇 |
2012年 | 1187篇 |
2011年 | 1113篇 |
2010年 | 644篇 |
2009年 | 574篇 |
2008年 | 724篇 |
2007年 | 682篇 |
2006年 | 556篇 |
2005年 | 509篇 |
2004年 | 487篇 |
2003年 | 348篇 |
2002年 | 302篇 |
2001年 | 129篇 |
2000年 | 114篇 |
1999年 | 85篇 |
1998年 | 36篇 |
1997年 | 39篇 |
1996年 | 25篇 |
1995年 | 23篇 |
1994年 | 19篇 |
1993年 | 13篇 |
1992年 | 22篇 |
1991年 | 29篇 |
1990年 | 19篇 |
1989年 | 13篇 |
1988年 | 16篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1973年 | 4篇 |
1971年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 421 毫秒
41.
Jan Hendrickx Paul Coucke Marie-Claude Hors-Cayla G. Peter A. Smit Yoon S. Shin Johann Deutsch Jan Smeitink Ruud Berger Philip Lee John Fernandes Patrick J. Willems 《Genomics》1994,21(3)
We describe here a new type of X-linked liver glycogen storage disease. The main symptoms include liver enlargement and growth retardation. The clinical and biochemical abnormalities of this glycogenosis are similar to those of classical X-linked liver glycogenosis due to phosphorylase kinase deficiency (XLG). However, in contrast to patients with XLG, the patients described here have no reduced phosphorylase kinase activity in erythrocytes and leukocytes, and no enzyme deficiency could be found. Linkage analysis of four families with this X-linked type of liver glycogenosis assigned the disease gene to Xp22. Lod scores obtained with the markers DXS987, DXS207, and DXS999 were 3.97, 2.71, and 2.40, respectively, all at 0% recombination. Multipoint linkage analysis localized the disease gene between DXS143 and DXS989 with a maximum lod score of 4.70 at θ = 0, relative to DXS987. As both the classical XLG gene and the liver α-subunit of PHK (PHKA2) are also located in Xp22, this variant type of XLG may be allelic to classical XLG, and both diseases may be caused by mutations in PHKA2. Therefore, we propose to classify XLG as XLG type I (the classical type of XLG) and XLG type II (the variant type of XLG). 相似文献
42.
43.
Jessica N. Hightower Dolly L. Crawford Wayne E. Thogmartin Kyle R. Aldinger Sara Barker Swarthout David A. Buehler John Confer Christian Friis Jeffery L. Larkin James D. Lowe Martin Piorkowski Ronald W. Rohrbaugh Kenneth V. Rosenberg Curtis Smalling Petra B. Wood Rachel Vallender Amber M. Roth 《Diversity & distributions》2023,29(2):254-271
Aim
Climate change is affecting the distribution of species and subsequent biotic interactions, including hybridization potential. The imperiled Golden-winged Warbler (GWWA) competes and hybridizes with the Blue-winged Warbler (BWWA), which may threaten the persistence of GWWA due to introgression. We examined how climate change is likely to alter the breeding distributions and potential for hybridization between GWWA and BWWA.Location
North America.Methods
We used GWWA and BWWA occurrence data to model climatically suitable conditions under historical and future climate scenarios. Models were parameterized with 13 bioclimatic variables and 3 topographic variables. Using ensemble modeling, we estimated historical and modern distributions, as well as a projected distribution under six future climate scenarios. We quantified breeding distribution area, the position of and amount of overlap between GWWA and BWWA distributions under each climate scenario. We summarized the top explanatory variables in our model to predict environmental parameters of the distributions under future climate scenarios relative to historical climate.Results
GWWA and BWWA distributions are projected to substantially change under future climate scenarios. GWWA are projected to undergo the greatest change; the area of climatically suitable breeding season conditions is expected to shift north to northwest; and range contraction is predicted in five out of six future climate scenarios. Climatically suitable conditions for BWWA decreased in four of the six future climate scenarios, while the distribution is projected to shift east. A reduction in overlapping distributions for GWWA and BWWA is projected under all six future climate scenarios.Main Conclusions
Climate change is expected to substantially alter the area of climatically suitable conditions for GWWA and BWWA, with the southern portion of the current breeding ranges likely to become climatically unsuitable. However, interactions between BWWA and GWWA are expected to decline with the decrease in overlapping habitat, which may reduce the risk of genetic introgression. 相似文献44.
Regulation of Saccharomyces cerevisiae CDC7 function during the cell cycle. 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The yeast Cdc7 function is required for the G1/S transition and is dependent on passage through START, a point controlled by the Cdc28/cdc2/p34 protein kinase. CDC7 encodes a protein kinase activity, and we now show that this kinase activity varies in the cell cycle but that protein levels appear to remain constant. We present several lines of evidence that periodic activation of CDC7 kinase is at least in part through phosphorylation. First, the kinase activity of the Cdc7 protein is destroyed by dephosphorylation of the protein in vitro with phosphatase. Second, Cdc7 protein is hypophosphorylated and inactive as a kinase in extracts of cells arrested at START but becomes active and maximally phosphorylated subsequent to passage through START. The phosphorylation pattern of Cdc7 protein is complex. Phosphopeptide mapping reveals four phosphopeptides in Cdc7 prepared from asynchronous yeast cells. Both autophosphorylation and phosphorylation in trans appear to contribute to this pattern. Autophosphorylation is shown to occur by using a thermolabile Cdc7 protein. A protein in yeast extracts can phosphorylate and activate Cdc7 protein made in Escherichia coli, and phosphorylation is thermolabile in cdc28 mutant extracts. Cdc7 protein carrying a serine to alanine change in the consensus recognition site for Cdc28 kinase shows an altered phosphopeptide map, suggesting that this site is important in determining the overall Cdc7 phosphorylation pattern. 相似文献
45.
46.
David Julian Arias-Chávez Patrick Mailloux-Salinas Jessica Ledesma Aparicio Elihu Campos-Pérez Omar Noel Medina-Campos José Pedraza-Chaverri Guadalupe Bravo 《Journal of cellular and molecular medicine》2023,27(20):3147-3156
Benign prostatic hyperplasia (BPH) is the most common adenoma in old men. Tomatoes are a rich source of bioactive compounds that, as well as selenium (Se), possess antioxidant and antiproliferative activity. The aim was to evaluate the therapeutic effect of Se in combination with a tomato extract in aged rats with BPH. Aged male Wistar rats were divided in the following groups (n = 10 rats/group): Control (C), BPH, BPH + Finasteride (BPH + F), BPH + Tomato Lipidic Extract (BPH + E), BPH + Selenium (BPH + S) and BPH plus E plus S (BPH + E + S). After 4 weeks of treatment, prostate weight, diuresis, antioxidants enzymes, prooxidants and inflammatory markers, growth factors and androgens were determined. BPH + E + S reduced prostate weight by 59.29% and inhibited growth by 99.35% compared to BPH + F which only decreased weight and inhibited growth by 15.31% and 57.54%, respectively. Prooxidant markers were higher with BPH + F (49.4% higher vs. BPH), but BPH + E + S decreased these markers (94.27% vs. BPH) and increased antioxidant activity. Finally, diuresis was higher with the BPH + E + S combination and markers of inflammation and growth factors were significantly lower with respect to BPH + F. Our findings provide a beneficial and protective therapeutic option of E + S directed against androgens, oxidative stress and inflammation that regulates cell proliferation in the prostate gland. 相似文献
47.
Francesca Vittoria Sbrana Benedetta Fiordi Jessica Bordini Daniela Belloni Federica Barbaglio Luca Russo Lydia Scarfò Paolo Ghia Cristina Scielzo 《Journal of cellular and molecular medicine》2023,27(4):576-586
Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose–response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy. 相似文献
48.
Matteo Zurlo Francesco Nicoli Davide Proietto Beatrice Dallan Cristina Zuccato Lucia Carmela Cosenza Jessica Gasparello Chiara Papi Elisabetta d'Aversa Monica Borgatti Chiara Scapoli Alessia Finotti Roberto Gambari 《Journal of cellular and molecular medicine》2023,27(3):353-364
Inhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. β-Thalassemia). The objective of the present study was to analyse the activity of CD4+ and CD8+ T cells in β-Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the NCT03877809 clinical trial. The approach was to verify IFN-γ releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4+ and CD8+ T cells, respectively. The main results of the present study are that treatment of β-Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4+ and CD8+ T cells releasing IFN-γ following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that β-Thalassemia patients are considered prone to immune deficiency. 相似文献
49.
Many tropical animals inhabit mosaic landscapes including human-modified habitat. In such landscapes, animals commonly adjust feeding behavior, and may incorporate non-natural foods. These behavioral shifts can influence consumers' nutritional states, with implications for population persistence. However, few studies have addressed the nutritional role of non-natural food. We examined nutritional ecology of wild blue monkeys to understand how dietary habits related to non-natural foods might support population persistence in a mosaic landscape. We documented prevalence and nutritional composition of non-natural foods in monkey diets to assess how habitat use influenced their consumption, and their contribution to nutritional strategies. While most energy and macronutrients came from natural foods, subjects focused non-natural feeding activity on five exotic plants, and averaged about a third of daily calories from non-natural foods. Most non-natural food calories came from non-structural carbohydrates and least from protein. Consumption of non-natural foods related to time in human-modified habitats, which two groups used non-randomly. Non-natural and natural foods were similar in nutrients, and the amount of non-natural food consumed drove variation in nutritional strategy. When more daily calories came from non-natural foods, females consumed a higher ratio of non-protein energy to protein (NPE:P). Females also prioritized protein while allowing NPE:P to vary, increasing NPE while capitalizing on non-natural foods. Overall, these tropical mammals achieved a similar nutrient balance regardless of their intake of non-natural foods. Forest and forest-adjacent areas with non-natural vegetation may provide adequate nutrient access for consumers, and thus contribute to wildlife conservation in mosaic tropical landscapes. 相似文献
50.
Arpana Agrawal Sarah J. Brislin Kathleen K. Bucholz Danielle Dick Ronald P. Hart Emma C. Johnson Jacquelyn Meyers Jessica Salvatore Paul Slesinger COGA Collaborators Laura Almasy Tatiana Foroud Alison Goate Victor Hesselbrock John Kramer Samuel Kuperman Alison K. Merikangas John I. Nurnberger Jay Tischfield Howard J. Edenberg Bernice Porjesz 《Genes, Brain & Behavior》2023,22(5):e12864