全文获取类型
收费全文 | 1978篇 |
免费 | 195篇 |
国内免费 | 1篇 |
出版年
2021年 | 19篇 |
2020年 | 15篇 |
2018年 | 19篇 |
2017年 | 15篇 |
2016年 | 32篇 |
2015年 | 61篇 |
2014年 | 57篇 |
2013年 | 71篇 |
2012年 | 106篇 |
2011年 | 86篇 |
2010年 | 54篇 |
2009年 | 64篇 |
2008年 | 83篇 |
2007年 | 75篇 |
2006年 | 86篇 |
2005年 | 78篇 |
2004年 | 58篇 |
2003年 | 60篇 |
2002年 | 89篇 |
2001年 | 72篇 |
2000年 | 79篇 |
1999年 | 53篇 |
1998年 | 30篇 |
1997年 | 24篇 |
1996年 | 23篇 |
1995年 | 16篇 |
1994年 | 23篇 |
1993年 | 18篇 |
1992年 | 51篇 |
1991年 | 48篇 |
1990年 | 40篇 |
1989年 | 38篇 |
1988年 | 41篇 |
1987年 | 30篇 |
1986年 | 29篇 |
1985年 | 37篇 |
1984年 | 25篇 |
1983年 | 21篇 |
1982年 | 19篇 |
1981年 | 17篇 |
1979年 | 27篇 |
1978年 | 11篇 |
1977年 | 21篇 |
1976年 | 19篇 |
1974年 | 14篇 |
1973年 | 11篇 |
1972年 | 18篇 |
1971年 | 17篇 |
1969年 | 21篇 |
1967年 | 11篇 |
排序方式: 共有2174条查询结果,搜索用时 187 毫秒
991.
992.
The notochord is one of the defining features of chordates. The ascidian notochord is a rod like structure consisting of a single row of 40 cells. The anterior 32 ;primary' notochord cells arise from the A-line (anterior vegetal) blastomeres of the eight-cell stage embryo, whereas the posterior 8 ;secondary' notochord cells arise from the B-line (posterior vegetal) blastomeres of the eight-cell stage embryo. Specification of notochord precursors within these two lineages occurs in a spatially and temporally distinct manner. We show that specification of the secondary but not the primary notochord in Ciona intestinalis requires a relay mechanism involving two signalling pathways. First, we show evidence that acquisition of secondary notochord fate is dependent upon lateral Nodal signalling sources, situated in the adjacent b-line animal cells. Expression of the notochord specific gene Ci-Brachyury in the secondary notochord precursor was downregulated following selective inhibition of Nodal signal reception in B-line derivatives and also, strikingly, following selective inhibition of Nodal signal reception in A-line cell derivatives. Within the A-line, Nodal signals are required for localised expression of Delta2, which encodes a divergent form of Delta ligand. Using four distinct reagents to inhibit Delta2/Notch signals, we showed that Delta2 signalling from A-line cells, which activates the Notch/Su(H) pathway in adjacent B-line cells, is required for specification of the secondary notochord precursor. We propose a model whereby laterally produced Nodal acts to specify the secondary notochord precursor both directly in the B-line cells and via Delta2 induction in adjacent A-line cells. 相似文献
993.
Levels of parasitism and the dynamics of helminth systems is subject to the impact of environmental conditions such that we may expect long term increases in temperature will increase the force of infection and the parasite's basic reproduction number, R0. We postulate that an increase in the force of infection will only lead to an increase in mean intensity of adults when adult parasite mortality is not determined by acquired immunity. Preliminary examination of long term trends of parasites of rabbits and grouse confirm these predictions. Parasite development rate increases with temperature and while laboratory studies indicate this is linear some recent studies indicate that this may be non-linear and would have an important impact on R0. Warming would also reduce the selective pressure for the development of arrestment and this would increase R0 so that in systems like the grouse and Trichostrongylus tenuis this would increase the instability and lead to larger disease outbreaks. Extreme climatic events that act across populations appear important in synchronizing transmission and disease outbreaks, so it is speculated that climate disruption will lead to increased frequency and intensity of disease outbreaks in parasite populations not regulated by acquired immunity. 相似文献
994.
Brett A. Goodman Simon C. Hudson Joanne L. Isaac Lin Schwarzkopf 《Evolution; international journal of organic evolution》2009,63(5):1279-1291
Body size and shape are primary determinants of reproductive output in a variety of taxa, so selection favoring specific body sizes and shapes may, in turn, have a direct affect on reproductive output, and ultimately fitness. In reptiles, species that occupy rocky habitats are often flattened, a morphological character that aids locomotion and life on rocks, but which may constrain reproductive output by reducing the amount of abdominal space available to fill with eggs or offspring. Using 20 species of tropical skink from a wide range of habitats, we quantified habitat use, body height, body volume, and reproductive output, to determine whether the evolution of a flattened body was correlated with a reduction in abdominal volume, and, in turn, with reduced reproductive output. In this group of lizards, the occupation of rocky habitats has led (1) to the evolution of a flattened body, and this shift in body shape has (2) caused a reduction in abdominal volume. Despite this reduction in abdominal volume reproductive output was unaffected, as flatter species compensate by being more "full" of eggs. Thus, we demonstrate that morphological adaptation for enhanced performance in specific habitats did not cause a reduction in instantaneous reproductive output. 相似文献
995.
Jones MA Ng BG Bhide S Chin E Rhodenizer D He P Losfeld ME He M Raymond K Berry G Freeze HH Hegde MR 《American journal of human genetics》2012,90(2):363-368
Congenital disorders of glycosylation (CDG) are inherited autosomal-recessive diseases that impair N-glycosylation. Approximately 20% of patients do not survive beyond the age of 5 years old as a result of widespread organ dysfunction. Although most patients receive a CDG diagnosis based on abnormal glycosylation of transferrin, this test cannot provide a genetic diagnosis; indeed, many patients with abnormal transferrin do not have mutations in any known CDG genes. Here, we combined biochemical analysis with whole-exome sequencing (WES) to identify the genetic defect in an untyped CDG patient, and we found a 22 bp deletion and a missense mutation in DDOST, whose product is a component of the oligosaccharyltransferase complex that transfers the glycan chain from a lipid carrier to nascent proteins in the endoplasmic reticulum lumen. Biochemical analysis with three biomarkers revealed that N-glycosylation was decreased in the patient's fibroblasts. Complementation with wild-type-DDOST cDNA in patient fibroblasts restored glycosylation, indicating that the mutations were pathological. Our results highlight the power of combining WES and biochemical studies, including a glyco-complementation system, for identifying and confirming the defective gene in an untyped CDG patient. This approach will be very useful for uncovering other types of CDG as well. 相似文献
996.
Ng BG Hackmann K Jones MA Eroshkin AM He P Wiliams R Bhide S Cantagrel V Gleeson JG Paller AS Schnur RE Tinschert S Zunich J Hegde MR Freeze HH 《American journal of human genetics》2012,90(4):685-688
CHIME syndrome is characterized by colobomas, heart defects, ichthyosiform dermatosis, mental retardation (intellectual disability), and ear anomalies, including conductive hearing loss. Whole-exome sequencing on five previously reported cases identified PIGL, the de-N-acetylase required for glycosylphosphatidylinositol (GPI) anchor formation, as a strong candidate. Furthermore, cell lines derived from these cases had significantly reduced levels of the two GPI anchor markers, CD59 and a GPI-binding toxin, aerolysin (FLAER), confirming the pathogenicity of the mutations. 相似文献
997.
Li J Wong CL Vijayasankaran N Hudson T Amanullah A 《Biotechnology and bioengineering》2012,109(5):1173-1186
Lactate has long been regarded as one of the key metabolites of mammalian cell cultures. High levels of lactate have clear negative impacts on cell culture processes, and therefore, a great amount of efforts have been made to reduce lactate accumulation and/or to induce lactate consumption in the later stage of cultures. However, there is virtually no report on the impact of lactate depletion after initial accumulation. In this work, we observed that glucose uptake rate dropped over 50% at the onset of lactate consumption, and that catabolism of alanine due to lactate depletion led to ammonium accumulation. We explored the impact of feeding lactate as well as pyruvate to the cultures. In particular, a strategy was employed where CO(2) was replaced by lactic acid for culture pH control, which enabled automatic lactate feeding. The results demonstrated that lactate or pyruvate can serve as an alternative or even preferred carbon source during certain stage of the culture in the presence of glucose, and that by feeding lactate or pyruvate, very low levels of ammonia can be achieved throughout the culture. In addition, low levels of pCO(2) were also maintained in these cultures. This was in strong contrast to the control cultures where lactate was depleted during the culture, and ammonia and pCO(2) build-up were significant. Culture growth and productivity were similar between the control and lactate-fed cultures, as well as various product quality attributes. To our knowledge, this work represents the first comprehensive study on lactate depletion and offers a simple yet effective strategy to overcome ammonia and pCO(2) accumulation that could arise in certain cultures due to early depletion of lactate. 相似文献
998.
Methylobacterium sp. strain GXF4 is an isolate from grapevine. Here we present the sequence, assembly, and annotation of its genome, which may shed light on its role as a grapevine xylem inhabitant. To our knowledge, this is the first genome announcement of a plant xylem-associated strain of the genus Methylobacterium. 相似文献
999.
Han Ming Gan Sean E. McGroty Teong Han Chew Kok Gan Chan Larry J. Buckley Michael A. Savka André O. Hudson 《Journal of bacteriology》2012,194(21):5981-5982
Enterobacter sp. strain SST3 is an endophytic bacterium isolated from Saccharum spp. Here we present its annotated draft genome that may shed light on its role as a bacterial endophyte of sugarcane. To our knowledge, this is the first genome announcement of a sugarcane-associated bacterium from the genus Enterobacter. 相似文献
1000.
Many human inherited disorders cause protein N-glycosylation defects, but there are few cellular markers to test gene complementation for such defects. Plasma membrane glycoproteins are potential biomarkers because they may be reduced or even absent in plasma membranes of glycosylation-deficient cells. We combined stable isotope labeling by amino acids in cell culture (SILAC) with linear ion trap mass spectrometry (LTQ Orbitrap(TM)) to identify and quantify membrane proteins from wild-type CHO and glycosylation-deficient CHO (Lec9) cells. We identified 165 underrepresented proteins from 1447 unique quantified proteins, including 18 N-glycosylated plasma membrane proteins. Using various methods, we found that intercellular cell adhesion molecule 1 (ICAM-1) was reduced in Lec9 cells and in fibroblasts from 31 congenital disorder of glycosylation (CDG) patients compared with normal controls. Mannose supplementation of phosphomannose isomerase-deficient CDG-Ib (MPI-CDG) cells and complementation with PMM2 in PMM2-deficient CDG-Ia (PMM2-CDG) cells partially corrected hypoglycosylation based on increased ICAM-1 presence on the plasma membrane. These data indicate that ICAM-1 could be a useful hypoglycosylation biomarker to assess gene complementation of CDG-I patient cells and to monitor improved glycosylation in response to therapeutic drugs. 相似文献