全文获取类型
收费全文 | 3258篇 |
免费 | 331篇 |
专业分类
3589篇 |
出版年
2023年 | 22篇 |
2022年 | 29篇 |
2021年 | 80篇 |
2020年 | 42篇 |
2019年 | 50篇 |
2018年 | 58篇 |
2017年 | 44篇 |
2016年 | 64篇 |
2015年 | 135篇 |
2014年 | 130篇 |
2013年 | 171篇 |
2012年 | 202篇 |
2011年 | 212篇 |
2010年 | 114篇 |
2009年 | 121篇 |
2008年 | 152篇 |
2007年 | 157篇 |
2006年 | 146篇 |
2005年 | 136篇 |
2004年 | 117篇 |
2003年 | 104篇 |
2002年 | 95篇 |
2001年 | 70篇 |
2000年 | 58篇 |
1999年 | 65篇 |
1998年 | 40篇 |
1997年 | 38篇 |
1996年 | 22篇 |
1995年 | 21篇 |
1993年 | 24篇 |
1992年 | 48篇 |
1991年 | 45篇 |
1990年 | 56篇 |
1989年 | 47篇 |
1988年 | 38篇 |
1987年 | 36篇 |
1986年 | 33篇 |
1985年 | 36篇 |
1984年 | 25篇 |
1983年 | 33篇 |
1982年 | 41篇 |
1981年 | 22篇 |
1980年 | 19篇 |
1979年 | 30篇 |
1978年 | 35篇 |
1977年 | 25篇 |
1976年 | 25篇 |
1975年 | 17篇 |
1974年 | 16篇 |
1973年 | 23篇 |
排序方式: 共有3589条查询结果,搜索用时 15 毫秒
31.
A combination of light, scanning and transmission electron microscopy was used to investigate the morphology and ultrastructure of normal human spinal ligaments sampled from adult surgical specimens. The ligamenta flava consist mostly of dense elastic fibers, whereas the supraspinous and interspinous ligaments are preponderantly collagenous. In all ligaments, the collagen fascicles are characterized by a regular crimp structure. The inner collagen fibers of interspinous ligaments tend to be oriented parallel to the spinous processes while those of the peripheral layers run in postero-cranial direction. The presence of proteoglycan filaments is clearly demonstrated in all of the ligaments examined. They are mainly located at the d band of the collagen fibrils. These findings are discussed in relation to the function of the posterior ligamentous system. It is suggested that the interspinous ligaments are able to transmit tension from the thoracolumbar fascia to the spine. Finally, the spinal ligaments are thought to be involved in the control mechanism of the spine. 相似文献
32.
Maya Kunigo Christoph Buerth Denis Tielker Joachim F. Ernst 《Applied microbiology and biotechnology》2013,97(16):7357-7368
The yeast Candida utilis (also referred to as Torula) is used as a whole-cell food additive and as a recombinant host for production of intracellular molecules. Here, we report recombinant C. utilis strains secreting significant amounts of Candida antarctica lipase B (CalB). Native and heterologous secretion signals led to secretion of CalB into the growth medium; CalB was enzymatically active and it carried a short N-glycosyl chain lacking extensive mannosylation. Furthermore, CalB fusions to the C. utilis Gas1 cell wall protein led to effective surface display of enzymatically active CalB and of β-galactosidase. Secretory production in C. utilis was achieved using a novel set of expression vectors containing sat1 conferring nourseothricin resistance, which could be transformed into C. utilis, Pichia jadinii, Candida albicans, and Saccharomyces cerevisiae; C. utilis promoters including the constitutive TDH3 and the highly xylose-inducible GXS1 promoters allowed efficient gene expression. These results establish C. utilis as a promising host for the secretory production of proteins. 相似文献
33.
Aspland SE Ballatore C Castillo R Desharnais J Eustaquio T Goelet P Guo Z Li Q Nelson D Sun C Castellino AJ Newman MJ 《Bioorganic & medicinal chemistry letters》2006,16(19):5194-5198
In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel-thymidine and vinblastine-thymidine bi-functional conjugates are reported here. This work provides the first account of 'kinase-mediated trapping' of cancer therapeutics. 相似文献
34.
A 5-year illness of a child, characterized by recurrent bacterial infections and abnormal results of nitroblue tetrazolium dye reduction tests, was suggestive of chronic granulomatous disease but the illness terminated in overt myeloid leukemia. During this progression studies of leukocyte structure and metabolic activity revealed abnormalities that suggested the existence of a "preleukemic" state. 相似文献
35.
Fang Fang Zhang Regina M. Santella Mary Wolff Maya A. Kappil Steven B. Markowitz Alfredo Morabia 《Epigenetics》2012,7(6):606-614
Altered levels of global DNA methylation and gene silencing through methylation of promoter regions can impact cancer risk, but little is known about their environmental determinants. We examined the association between lifestyle factors and levels of global genomic methylation and IL-6 promoter methylation in white blood cell DNA of 165 cancer-free subjects, 18–78 years old, enrolled in the COMIR (Commuting Mode and Inflammatory Response) study, New York, 2009–2010. Besides self-administrated questionnaires on diet and physical activity, we measured weight and height, white blood cell (WBC) counts, plasma levels of high sensitivity C-reactive protein (hs-CRP), and genomic (LINE-1) and gene-specific methylation (IL-6) by pyrosequencing in peripheral blood WBC. Mean levels of LINE-1 and IL-6 promoter methylation were 78.2% and 57.1%, respectively. In multivariate linear regression models adjusting for age, gender, race/ethnicity, body mass index, diet, physical activity, WBC counts and CRP, only dietary folate intake from fortified foods was positively associated with LINE-1 methylation. Levels of IL-6 promoter methylation were not significantly correlated with age, gender, race/ethnicity, body mass index, physical activity or diet, including overall dietary patterns and individual food groups and nutrients. There were no apparent associations between levels of methylation and inflammation markers such as WBC counts and hs-CRP. Overall, among several lifestyle factors examined in association with DNA methylation, only dietary folate intake from fortification was associated with LINE-1 methylation. The long-term consequence of folate fortification on DNA methylation needs to be further evaluated in longitudinal settings. 相似文献
36.
Ileana Manduteanu Dan Simionescu Agneta Simionescu Maya Simionescu 《Journal of cellular and molecular medicine》2021,25(20):9483-9495
Valve disease and particularly calcific aortic valve disease (CAVD) and diabetes (DM) are progressive diseases constituting a global health burden for all aging societies (Progress in Cardiovascular Diseases. 2014;56(6):565: Circulation Research. 2021;128(9):1344). Compared to non-diabetic individuals (The Lancet. 2008;371(9626):1800: The American Journal of Cardiology. 1983;51(3):403: Journal of the American College of Cardiology. 2017;69(12):1523), the diabetic patients have a significantly greater propensity for cardiovascular disorders and faster degeneration of implanted bioprosthetic aortic valves. Previously, using an original experimental model, the diabetic-hyperlipemic hamsters, we have shown that the earliest alterations induced by these conditions occur at the level of the aortic valves and, with time these changes lead to calcifications and CAVD. However, there are no pharmacological treatments available to reverse or retard the progression of aortic valve disease in diabetes, despite the significant advances in the field. Therefore, it is critical to uncover the mechanisms of valve disease progression, find biomarkers for diagnosis and new targets for therapies. This review aims at presenting an update on the basic research in CAVD in the context of diabetes. We provide an insight into the accumulated data including our results on diabetes-induced progressive cell and molecular alterations in the aortic valve, new potential biomarkers to assess the evolution and therapy of the disease, advancement in targeted nanotherapies, tissue engineering and the potential use of circulating endothelial progenitor cells in CAVD. 相似文献
37.
Víctor Faundes William G. Newman Laura Bernardini Natalie Canham Jill Clayton-Smith Bruno Dallapiccola Sally J. Davies Michelle K. Demos Amy Goldman Harinder Gill Rachel Horton Bronwyn Kerr Dhavendra Kumar Anna Lehman Shane McKee Jenny Morton Michael J. Parker Julia Rankin Siddharth Banka 《American journal of human genetics》2018,102(1):175-187
38.
Epithelial cells isolated from rat lung and trachea were grown on monolayers and their response to a number of hormones and
growth factors were studied. Maximum proliferative response in serum containing media was observed when insulin, cholera toxin
and cortisol were present together. However, these additives when present independently showed a marginal response. The synergism,
due to these factors in promoting growth was seen very early in culture (day 4) as shown by thymidine labelling studies, On
examining the indices of early mitogenesis, such as the expression ofc-myc, our data suggests that these factors stimulate the expression ofc-myc within 4 h. With respect to expression of TNF-α mRNA, this study suggests a possible modulation of TNF-α expression in response
to these mitogens that stimulate proliferation maximally. Whether this expression of TNF-α by these epithelial cells is due
to a maximal proliferative stimulus and/or is an early step in the cascade of intracellular signalling events is to be investigated
in detail. 相似文献
39.
Plants produce proximal-distal growth axes with two types of growth potential: they can be indeterminate, in which case growth continues indefinitely, or they can be determinate, in which case growth is limited to the production of a single organ or a discrete set of organs. The indeterminate shoot axes of Arabidopsis pinhead/zwille mutants frequently are transformed to a determinate state. PINHEAD (PNH) is expressed in the central domain of the developing plant: the provascular tissue, the shoot apical meristem, and the adaxial (upper) sides of lateral organ primordia. Here, we show that ectopic expression of PNH on the abaxial (lower) sides of lateral organs results in upward curling of leaf blades. This phenotype correlates with a loss of cell number coordination between the two surfaces of the blade, indicating that ectopic PNH can cause changes in cell division rates. More strikingly, moving PNH expression from the central to the peripheral domain of the embryo causes transformation of the determinate cotyledon axis to an indeterminate state. We propose that growth axes are specified as determinate versus indeterminate in a PNH-mediated step. Our results add to a growing body of evidence that radial positional information is important in meristem formation. These results also indicate that genes regulating cell division and axis determinacy are likely to be among PNH targets. 相似文献
40.
Dissection of Nodule Development by Supplementation of Rhizobium leguminosarum biovar phaseoli Purine Auxotrophs with 4-Aminoimidazole-5-Carboxamide Riboside 总被引:2,自引:0,他引:2 下载免费PDF全文
Purine auxotrophs of Rhizobium leguminosarum biovar phaseoli CFN42 elicit uninfected pseudonodules on bean (Phaseolus vulgaris L.). Addition of 4-aminoimidazole-5-carboxamide (AICA) riboside to the root medium during incubation of the plant with these mutants leads to enhanced nodule development, although nitrogenase activity is not detected. Nodules elicited in this manner had infection threads and anatomical features characteristic of normal nodules, such as peripheral vasculature rather than the central vasculature of the pseudonodules that were elicited without AICA riboside supplementation. Although 105 to 106 bacteria could be recovered from these nodules after full development, bacteria were not observed in the interior nodule cells. Instead, large cells with extensive internal membranes were present. Approximately 5% of the normal amount of leghemoglobin and 10% of the normal amount of uricase were detected in these nodules. To promote the development of true nodules rather than pseudonodules, AICA riboside was required no later than the second day through no more than the sixth day following inoculation. After this period, removal of AICA riboside from the root medium did not prevent the formation of true nodules. This observation suggests that there is a critical stage of infection, reached before nodule emergence, at which development becomes committed to forming a true nodule rather than a pseudonodule. 相似文献