全文获取类型
收费全文 | 4573篇 |
免费 | 391篇 |
国内免费 | 1篇 |
出版年
2023年 | 20篇 |
2022年 | 64篇 |
2021年 | 114篇 |
2020年 | 60篇 |
2019年 | 103篇 |
2018年 | 103篇 |
2017年 | 102篇 |
2016年 | 151篇 |
2015年 | 247篇 |
2014年 | 262篇 |
2013年 | 289篇 |
2012年 | 371篇 |
2011年 | 380篇 |
2010年 | 213篇 |
2009年 | 198篇 |
2008年 | 256篇 |
2007年 | 287篇 |
2006年 | 230篇 |
2005年 | 227篇 |
2004年 | 177篇 |
2003年 | 209篇 |
2002年 | 187篇 |
2001年 | 49篇 |
2000年 | 28篇 |
1999年 | 45篇 |
1998年 | 46篇 |
1997年 | 34篇 |
1996年 | 28篇 |
1995年 | 22篇 |
1994年 | 26篇 |
1993年 | 35篇 |
1992年 | 32篇 |
1991年 | 31篇 |
1990年 | 19篇 |
1989年 | 28篇 |
1988年 | 22篇 |
1987年 | 24篇 |
1986年 | 17篇 |
1985年 | 28篇 |
1984年 | 16篇 |
1983年 | 16篇 |
1981年 | 13篇 |
1979年 | 12篇 |
1978年 | 9篇 |
1977年 | 9篇 |
1976年 | 11篇 |
1975年 | 10篇 |
1973年 | 15篇 |
1972年 | 12篇 |
1971年 | 13篇 |
排序方式: 共有4965条查询结果,搜索用时 15 毫秒
171.
172.
Thomas Clavel Hans-Peter Horz Nicola Segata Maria Vehreschild 《Microbial biotechnology》2022,15(1):164-175
Gut microbiome research has bloomed over the past 15 years. We have learnt a lot about the complex microbial communities that colonize our intestine. Promising avenues of research and microbiome-based applications are being implemented, with the goal of sustaining host health and applying personalized disease management strategies. Despite this exciting outlook, many fundamental questions about enteric microbial ecosystems remain to be answered. Organizational measures will also need to be taken to optimize the outcome of discoveries happening at an extremely rapid pace. This article highlights our own view of the field and perspectives for the next 15 years. 相似文献
173.
The FDA has published guidelines by which to carry out and interpret in vitro induction studies using hepatocytes but do researchers in pharmaceutical companies actually follow these to the letter? In a survey of 30 participants in the pharmaceutical industry, 19 questions were posed regarding the species investigated, methodologies and interpretations of the data. Also addressed was the in-house decision making processes as a result of in vitro induction data. The survey showed that, although the basic methods were similar, no two researchers carried out and interpreted induction assays in exactly the same way. No single method was superior but all included enzyme activities as the major end point. Hepatocytes from animal species were used to confirm animal in vivo data but only human hepatocytes were used to predict human induction responses. If a compound was found to be positive in an in vitro induction assay, few would halt the development of the compound. The majority would consider other properties of the compound (bioavailability, clearance and therapeutic concentrations) and follow the FDA recommendation to conduct clinical drug-drug interaction studies. Overall, the results from this survey indicate that there is no standard pharmaceutical industry method or evaluation criterion by which in vitro assays are carried out. Rather than adhering to the FDA guidelines, some adapt methods and interpretation according to their own experience and need (whether screening or lead optimisation). There was general consensus that studies using human hepatocyte cultures currently provide the best indication of the in vivo induction potential of NCEs. In addition, the assessment of in vitro induction data from the literature suggest that the two-fold induction threshold and the percent of positive control criteria may not be the best methods to accurately assess the in vivo induction potential of a drug. Although the two-fold induction criterion is now obsolete, more predictive models for determining the clinical induction potential are needed. Alternative models are proposed and discussed herein. 相似文献
174.
Endoglin is required for myogenic differentiation potential of neural crest stem cells 总被引:1,自引:0,他引:1
Mancini ML Verdi JM Conley BA Nicola T Spicer DB Oxburgh LH Vary CP 《Developmental biology》2007,308(2):520-533
Genetic studies show that TGFbeta signaling is essential for vascular development, although the mechanism through which this pathway operates is incompletely understood. Here we demonstrate that the TGFbeta auxiliary coreceptor endoglin (eng, CD105) is expressed in a subset of neural crest stem cells (NCSCs) in vivo and is required for their myogenic differentiation. Overexpression of endoglin in the neural crest caused pericardial hemorrhaging, correlating with altered vascular smooth muscle cell investment in the walls of major vessels and upregulation of smooth muscle alpha-actin protein levels. Clonogenic differentiation assay of NCSCs derived from neural tube explants demonstrated that only NCSC expressing high levels of endoglin (NCSC(CD105+)) had myogenic differentiation potential. Furthermore, myogenic potential was deficient in NCSCs obtained from endoglin null embryos. Expression of endoglin in NCSCs declined with age, coinciding with a reduction in both smooth muscle differentiation potential and TGFbeta1 responsiveness. These findings demonstrate a cell autonomous role for endoglin in smooth muscle cell specification contributing to vascular integrity. 相似文献
175.
Functional roles for beta1,4-N-acetlygalactosaminyltransferase-A in Drosophila larval neurons and muscles 下载免费PDF全文
Adult Drosophila mutant for the glycosyltransferase beta1,4-N-acetlygalactosaminyltransferase-A (beta4GalNAcTA) display an abnormal locomotion phenotype, indicating a role for this enzyme, and the glycan structures that it generates, in the neuromuscular system. To investigate the functional role of this enzyme in more detail, we turned to the accessible larval neuromuscular system and report here that larvae mutant for beta4GalNAcTA display distinct nerve and muscle phenotypes. Mutant larvae exhibit abnormal backward crawling, reductions in nerve terminal bouton number, decreased spontaneous transmitter-release frequency, and short, wide muscles. This muscle shape change appears to result from hypercontraction since the individual sarcomeres are shorter in mutant muscles. Analysis of muscle calcium signals showed altered calcium handling in the mutant, suggesting a mechanism by which hypercontraction could occur. All of these phenotypes can be rescued by a transgene carrying the beta4GalNAcTA genomic region. Tissue-specific expression, using the Gal4-UAS system, reveals that neural expression rescues the mutant crawling phenotype, while muscle expression rescues the muscle defect. Tissue-specific expression did not appear to rescue the decrease in neuromuscular junction bouton number, suggesting that this defect arises from cooperation between nerve and muscle. Altogether, these results suggest that beta4GalNAcTA has at least three distinct functional roles. 相似文献
176.
Greater bone formation of Y2 knockout mice is associated with increased osteoprogenitor numbers and altered Y1 receptor expression 总被引:4,自引:0,他引:4
177.
178.
179.
180.
During in vivo tissue regeneration, cell behavior is highly influenced by the surrounding environment. Thus, the choice of scaffold material and its microstructure is one of the fundamental steps for a successful in vitro culture. An efficacious method for scaffold fabrication should prove its versatility and the possibility of controlling micro- and nanostructure. In this paper, hyaluronic acid 3D scaffolds were developed through lamination of micropatterned membranes, fabricated after optimization of a soft-lithography method. The scaffold presented here is characterized by a homogeneous hexagonal lattice with porosity of 69%, specific surface area of 287 cm-1, and permeability of 18.9 microm2. The control over the geometry was achieved with an accuracy of 20 mum. This technique allowed not only fabrication of planar 3D scaffolds but also production of thin wall tubular constructs. Mechanical tests, performed on dry tubular scaffolds, show high rupture tensile strength. This construct could be promising not only as engineered vascular grafts but also for regeneration of skin, urethra, and intestinal walls. The biocompatibility of a 3D planar scaffold was tested by seeding human fibroblasts. The cells were cultured in both static and dynamic conditions, in a perfusion bioreactor at different flow rates. Microscope analysis and MTT test showed cell proliferation and viability and a uniform cell distribution likely due to an appropriate lattice structure. 相似文献