全文获取类型
收费全文 | 1287篇 |
免费 | 105篇 |
国内免费 | 1篇 |
专业分类
1393篇 |
出版年
2022年 | 10篇 |
2021年 | 15篇 |
2019年 | 19篇 |
2017年 | 11篇 |
2016年 | 28篇 |
2015年 | 42篇 |
2014年 | 42篇 |
2013年 | 69篇 |
2012年 | 61篇 |
2011年 | 66篇 |
2010年 | 42篇 |
2009年 | 37篇 |
2008年 | 44篇 |
2007年 | 56篇 |
2006年 | 51篇 |
2005年 | 46篇 |
2004年 | 47篇 |
2003年 | 48篇 |
2002年 | 42篇 |
2001年 | 29篇 |
2000年 | 29篇 |
1999年 | 24篇 |
1998年 | 16篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 17篇 |
1991年 | 30篇 |
1990年 | 33篇 |
1989年 | 26篇 |
1988年 | 23篇 |
1987年 | 15篇 |
1986年 | 21篇 |
1985年 | 14篇 |
1984年 | 22篇 |
1983年 | 20篇 |
1982年 | 22篇 |
1981年 | 18篇 |
1980年 | 17篇 |
1979年 | 18篇 |
1978年 | 14篇 |
1977年 | 14篇 |
1976年 | 11篇 |
1974年 | 16篇 |
1973年 | 20篇 |
1972年 | 8篇 |
1971年 | 8篇 |
1970年 | 9篇 |
1966年 | 8篇 |
排序方式: 共有1393条查询结果,搜索用时 0 毫秒
131.
Leon A. Bach 《Journal of cell communication and signaling》2015,9(2):189-200
IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. IGFBP-6 also induces migration of tumour cells including rhabdomyosarcomas by an IGF-independent mechanism. This chemotactic effect is mediated by MAP kinases. IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. IGFBP-6 may enter the nucleus and modulate cell survival and differentiation. IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. 相似文献
132.
Swapnil A. Malekar Ashish L. Sarode Alvin C. Bach II Arijit Bose Geoffrey Bothun David R. Worthen 《AAPS PharmSciTech》2015,16(6):1335-1343
This work was conducted in order to design, characterize, and evaluate stable liposomes containing the hydrophobic drug raloxifene HCl (RAL) and hydrophilic doxycycline HCl (DOX), two potentially synergistic agents for treating osteoporosis and other bone lesions, in conjunction with a radio frequency-induced, hydrophobic magnetic nanoparticle-dependent triggering mechanism for drug release. Both drugs were successfully incorporated into liposomes by lipid film hydration, although combination drug loading compromised liposome stability. Liposome stability was improved by reducing the drug load and by including Pluronics® (PL) in the formulations. DOX did not appear to interact with the phospholipid membranes comprising the liposomes, and its release was maximized in the presence of radio frequency (RF) heating. In contrast, differential scanning calorimetry (DSC) and phosphorus-31 nuclear magnetic resonance (31P-NMR) analysis revealed that RAL developed strong interactions with the phospholipid membranes, most notably with lipid phosphate head groups, resulting in significant changes in membrane thermodynamics. Likewise, RAL release from liposomes was minimal, even in the presence of RF heating. These studies may offer useful insights into the design and optimization of multidrug containing liposomes. The effects of RAL on liposome characteristics and drug release performance underscore the importance of appropriate physical-chemical analysis in order to identify and characterize drug-lipid interactions that may profoundly affect liposome properties and performance early in the formulation development process.KEY WORDS: controlled release, drug combination, liposomes, nanoparticles 相似文献
133.
Y‐craniosynostosis by premature fusion of the metopic and coronal sutures: A new nosological entity or a variety of Saethre‐Chotzen syndrome?
下载免费PDF全文
![点击此处可从《Birth defects research. Part A, Clinical and molecular teratology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
134.
Kamilla Mundbjerg Signe W. J?rgensen Jacob Freds?e Ida Nielsen Jakob Madsen Pedersen Iben Bach Bentsen Michael Lisby Lotte Bjergbaek Anni H Andersen 《PLoS genetics》2015,11(12)
Faithful DNA replication with correct termination is essential for genome stability and transmission of genetic information. Here we have investigated the potential roles of Topoisomerase II (Top2) and the RecQ helicase Sgs1 during late stages of replication. We find that cells lacking Top2 and Sgs1 (or Top3) display two different characteristics during late S/G2 phase, checkpoint activation and accumulation of asymmetric X-structures, which are both independent of homologous recombination. Our data demonstrate that checkpoint activation is caused by a DNA structure formed at the strongest rDNA replication fork barrier (RFB) during replication termination, and consistently, checkpoint activation is dependent on the RFB binding protein, Fob1. In contrast, asymmetric X-structures are formed independent of Fob1 at less strong rDNA replication fork barriers. However, both checkpoint activation and formation of asymmetric X-structures are sensitive to conditions, which facilitate fork merging and progression of replication forks through replication fork barriers. Our data are consistent with a redundant role of Top2 and Sgs1 together with Top3 (Sgs1-Top3) in replication fork merging at rDNA barriers. At RFB either Top2 or Sgs1-Top3 is essential to prevent formation of a checkpoint activating DNA structure during termination, but at less strong rDNA barriers absence of the enzymes merely delays replication fork merging, causing an accumulation of asymmetric termination structures, which are solved over time. 相似文献
135.
Since its introduction by Georges Smith some 25 years ago, phage display has proved to be a powerful molecular technique for selecting proteins with desired biological properties from huge libraries. Early on, various protease inhibitor scaffolds were displayed at the surface of filamentous phages to select new inhibitors with shifted specificities and enhanced affinities towards one or more target protease(s). The past two decades have seen a number of natural protease inhibitors subjected to phage display, mostly to shift and increase their inhibitory specificity, but also to explore the molecular mechanisms by which they interact with their cognate enzymes with low or very high selectivity. This review focuses on the major uses of phage display in the field of protein protease inhibitors. The exquisite molecular mechanisms by which natural protease inhibitors prevent unwanted or excessive proteolysis in cells and tissues are also examined along with some of the general principles underlying the way phage display is applied to these molecules. 相似文献
136.
Fran?ois Roudier Lionel Gissot Frédéric Beaudoin Richard Haslam Louise Michaelson Jessica Marion Diana Molino Amparo Lima Liên Bach Halima Morin Frédérique Tellier Jean-Christophe Palauqui Yannick Bellec Charlotte Renne Martine Miquel Marco DaCosta Julien Vignard Christine Rochat Jonathan E. Markham Patrick Moreau Johnathan Napier Jean-Denis Faure 《The Plant cell》2010,22(2):364-375
Very-long-chain fatty acids (VLCFAs) are essential for many aspects of plant development and necessary for the synthesis of seed storage triacylglycerols, epicuticular waxes, and sphingolipids. Identification of the acetyl-CoA carboxylase PASTICCINO3 and the 3-hydroxy acyl-CoA dehydratase PASTICCINO2 revealed that VLCFAs are important for cell proliferation and tissue patterning. Here, we show that the immunophilin PASTICCINO1 (PAS1) is also required for VLCFA synthesis. Impairment of PAS1 function results in reduction of VLCFA levels that particularly affects the composition of sphingolipids, known to be important for cell polarity in animals. Moreover, PAS1 associates with several enzymes of the VLCFA elongase complex in the endoplasmic reticulum. The pas1 mutants are deficient in lateral root formation and are characterized by an abnormal patterning of the embryo apex, which leads to defective cotyledon organogenesis. Our data indicate that in both tissues, defective organogenesis is associated with the mistargeting of the auxin efflux carrier PIN FORMED1 in specific cells, resulting in local alteration of polar auxin distribution. Furthermore, we show that exogenous VLCFAs rescue lateral root organogenesis and polar auxin distribution, indicating their direct involvement in these processes. Based on these data, we propose that PAS1 acts as a molecular scaffold for the fatty acid elongase complex in the endoplasmic reticulum and that the resulting VLCFAs are required for polar auxin transport and tissue patterning during plant development. 相似文献
137.
Jens Rydell Lothar Bach Marie-Jo Dubourg-Savage Martin Green Luísa Rodrigues Anders Hedenström 《European Journal of Wildlife Research》2010,56(6):823-827
This note is based on a literature search and a recent review of bat mortality data from wind farms in Europe (published elsewhere).
We suggest that mortality of bats at wind turbines may be linked to high-altitude feeding on migrating insects that accumulate
at the turbine towers. Modern wind turbines seem to reach high enough into the airspace to interfere with the migratory movements
of insects. The hypothesis is consistent with recent observations of bats at wind turbines. It is supported by the observation
that mortality of bats at wind turbines is highly seasonal (August–September) and typically peaks during nights with weather
conditions known to trigger large-scale migratory movements of insects (and songbirds). We also discuss other current hypotheses
concerning the mortality of bats at wind turbines. 相似文献
138.
Cybele Esteves Almeida Barbara Charlotte Bach Maristela Lovato Flores Rogério Pereira Fontoura Stefanie Dickel Segabinazi Marta Helena Carlesso Aita 《European Journal of Wildlife Research》2010,56(1):101-104
Serum proteins from 47 healthy greater rheas (Rhea americana; male and female) were separated by electrophoresis in order to characterize normal reference ranges. Determination of total
protein concentration was performed through biuret reaction. The mean value of total serum protein was 4.4 g/dL. Absolute
concentrations of serum proteins were determined by agarose gel electrophoretic fractioning. Five fractions were analyzed:
albumin, alpha, beta1, beta2, and gamma globulins, and the average values in grams per deciliter were 2.39, 0.32, 0.45, 0.30,
and 0.79, respectively. 相似文献
139.
Very long chain fatty acids (VLCFAs) are essential components for eukaryotes. They are elongated by the elongase complex in the endoplasmic reticulum and are incorporated into four major lipid pools (triacylglycerols, waxes, phospholipids, complex sphingolipids). Functional analysis of several components of the elongase complex demonstrated the essential role of VLCFAs in plants, invertebrates and vertebrates. Although VLCFAs changes in the triacylglycerol pool has no consequence for plant development, modifications of the nature and levels of VLCFAs in waxes, phospholipids and complex sphingolipids have, collectively, profound effects on embryo, leaf, root and flower development. VLCFAs levels in epicuticular waxes are critical for the regulation of epidermal fusions during organogenesis. VLCFAs phospholipids and sphingolipids are involved in membrane structure and dynamics regulating cell size but also division and differentiation. This review summarizes the recent findings in plants but also in other organisms, highlighting the importance of very long acyl chain length during development. 相似文献
140.
Sonia Lewycka Charles Mwansambo Peter Kazembe Tambosi Phiri Andrew Mganga Mikey Rosato Hilda Chapota Florida Malamba Stefania Vergnano Marie-Louise Newell David Osrin Anthony Costello 《Trials》2010,11(1):1-15