全文获取类型
收费全文 | 4736篇 |
免费 | 316篇 |
专业分类
5052篇 |
出版年
2023年 | 22篇 |
2022年 | 56篇 |
2021年 | 95篇 |
2020年 | 54篇 |
2019年 | 88篇 |
2018年 | 94篇 |
2017年 | 90篇 |
2016年 | 124篇 |
2015年 | 194篇 |
2014年 | 228篇 |
2013年 | 325篇 |
2012年 | 431篇 |
2011年 | 380篇 |
2010年 | 230篇 |
2009年 | 198篇 |
2008年 | 323篇 |
2007年 | 299篇 |
2006年 | 298篇 |
2005年 | 248篇 |
2004年 | 253篇 |
2003年 | 232篇 |
2002年 | 173篇 |
2001年 | 52篇 |
2000年 | 35篇 |
1999年 | 38篇 |
1998年 | 58篇 |
1997年 | 38篇 |
1996年 | 52篇 |
1995年 | 34篇 |
1994年 | 28篇 |
1993年 | 25篇 |
1992年 | 28篇 |
1991年 | 29篇 |
1990年 | 13篇 |
1989年 | 15篇 |
1988年 | 12篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 14篇 |
1984年 | 14篇 |
1983年 | 12篇 |
1982年 | 19篇 |
1981年 | 11篇 |
1980年 | 10篇 |
1979年 | 9篇 |
1978年 | 10篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1971年 | 4篇 |
1941年 | 4篇 |
排序方式: 共有5052条查询结果,搜索用时 15 毫秒
61.
Mauro C Vito P Mellone S Pacifico F Chariot A Formisano S Leonardi A 《Biochemical and biophysical research communications》2003,309(1):84-90
Nuclear factor kappaB (NF-kappaB) plays a pivotal role in numerous cellular processes, including stress response, inflammation, and protection from apoptosis. Therefore, the activity of NF-kappaB needs to be tightly regulated. We have previously identified a novel gene, named CIKS (connection to IkappaB-kinase and SAPK), able to bind the regulatory sub-unit NEMO/IKKgamma and to activate NF-kappaB. Here, we demonstrate that CIKS forms homo-oligomers, interacts with NEMO/IKKgamma, and is recruited to the IKK-complex upon cell stimulation. In addition, we identified the regions of CIKS responsible for these functions. We found that the ability of CIKS to oligomerize, and to be recruited to the IKK-complex is not sufficient to activate the NF-kappaB. In fact, a deletion mutant of CIKS able to oligomerize, to interact with NEMO/IKKgamma, and to be recruited to the IKK-complex does not activate NF-kappaB, suggesting that CIKS needs a second level of regulation to efficiently activate NF-kappaB. 相似文献
62.
Montiel-Armendáriz Sharai Verdugo Claudio Juache-Villagrana Alan Esteban Jiménez-Vega Florinda Quezada-Casasola Andrés Vital-García Cuauhcihualt Escárcega-Ávila Angélica 《Experimental & applied acarology》2021,84(2):473-484
Experimental and Applied Acarology - In total, 57 ticks were collected from six white-tailed deer (Odocoileus virginianus) and three mule deer (O. hemionus) in northern Mexico during the 2017, 2018... 相似文献
63.
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that involve misfolding of the prion protein. Recent studies have provided evidence that normal prion protein might have a physiological function in neuroprotective signaling, suggesting that loss of prion protein activity might contribute to the pathogenesis of prion disease. However, studies using knockout animals do not support the loss-of-function hypothesis and argue that prion neurodegeneration might be associated with a gain of a toxic activity by the misfolded prion protein. Thus, the mechanism of neurodegeneration in spongiform encephalopathies remains enigmatic. 相似文献
64.
AN ELECTRON MICROSCOPE STUDY OF DENERVATION ATROPHY IN RED AND WHITE SKELETAL MUSCLE FIBERS 总被引:4,自引:0,他引:4 下载免费PDF全文
A study, mainly by electron microscopy, has been made on two leg muscles of rat, in the course of atrophy experimentally induced by total denervation. As a preliminary the chief distinctive features of the soleus, chosen as a representative of pure red muscle, and of the gastrocnemius, representative of pure white muscle, are described. Two major phases of atrophy, somewhat overlapping in time, were observed. In the first, a degenerative autolytic process takes place in areas of the fiber, with loss of striation. It can be detected as early as the 7th day, but the maximum is observed at the 14th day, and accounts for a gross weight loss of 50 per cent. The first alteration appears in the Z lines; disorder in the disposition of filaments then follows. The process occurs very rapidly, leaving large areas in the cell in which one can detect only ground substance, glycogen, rare randomly disposed vesicular elements, and some mitochondria. Several lysosomes and masses of lipoproteins, which assume the configuration of concentric lamellae, show up in these fibers. Subsequently large parts of the waste sarcoplasm are discarded into the intercellular spaces. In the second major phase the so called "simple" atrophy takes place. The process starts early, but its effects are more detectable after 1 month. In this period, single myofibrils undergo different degrees of reduction in diameter, while the spatial disposition of primary and secondary filaments inside the fibrils remains normal. The appearance of the fibrils in longitudinal sections suggests that the process takes place by the detachment of filaments from the periphery of the fibrils and by their subsequent breakdown in the interfibrillary spaces. The sarcoplasmic reticulum is still well preserved, and relatively overdeveloped. Mitochondria disappear in parallel with the contractile material. 相似文献
65.
Molecular phylogeography of Troglophilus cave crickets (Orthoptera,Rhaphidophoridae): A combination of vicariance and dispersal drove diversification in the East Mediterranean region 下载免费PDF全文
Giuliana Allegrucci Valerio Ketmaier Claudio Di Russo Mauro Rampini Valerio Sbordoni Marina Cobolli 《Journal of Zoological Systematics and Evolutionary Research》2017,55(4):310-325
In this study, we investigated the molecular phylogenetic divergence and historical biogeography of cave crickets belonging to the genus Troglophilus (Orthoptera, Rhaphidophoridae) from caves in eastern Mediterranean and Anatolia regions. Three mitochondrial DNA genes (COI, 12S rDNA, and 16S rDNA) and two nuclear ones (18S rDNA and 28S rDNA) were amplified and partially sequenced to reconstruct phylogenetic relationships among most of the known Troglophilus species. Results showed a well‐resolved phylogeny with three main clades representing the Balkan, the Anatolian, and the Cycladian–Cretan lineages. Based on Bayesian analyses, we applied a relaxed molecular clock model to estimate the divergence times between these three lineages. Dating estimates indicate that radiation of the ingroup might have been triggered by the opening of the Mid‐Aegean trench, while the uplift of the Anatolian Plateau in Turkey and the changes of relief, emergence, and disappearance of orographic and hydrographical barriers in the Balkan Peninsula are potential paleogeographic events responsible for the initial diversification of the genus Troglophilus. A possible biogeographic scenario, reconstructed using S‐DIVA with RASP software, suggested that the current distribution of Troglophilus species can be explained by a combination of both dispersal and vicariance events that occurred in particular in the ancestral populations. The radiation of Troglophilus species likely started from the Aegean and proceeded eastward to Anatolia and westward to the Balkan region. Results are additionally compared to those available for Dolichopoda, the only other representative genus of Rhaphidophoridae present in the Mediterranean area. 相似文献
66.
Stern CD Charité J Deschamps J Duboule D Durston AJ Kmita M Nicolas JF Palmeirim I Smith JC Wolpert L 《The International journal of developmental biology》2006,50(1):3-15
When, where and how is the head-tail axis of the embryo set up during development? These are such fundamental and intensely studied questions that one might expect them to have been answered long ago. Not so; we still understand very little about the cellular or molecular mechanisms that lead to the orderly arrangement of body elements along the head-tail axis in vertebrates. In this paper, we outline some of the major outstanding problems and controversies and try to identify some reasons why it has been so difficult to resolve this important issue. 相似文献
67.
68.
69.
Agneta L. Sunehag Chiara Dalla Man Gianna Toffolo Morey W. Haymond Dennis M. Bier Claudio Cobelli 《Obesity (Silver Spring, Md.)》2009,17(2):233-239
Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose‐tolerance test (OGTT). A minimal model method is proposed to measure quantitative indices of insulin secretion and action in adolescents from an oral test. A 7 h, 21‐sample OGTT was performed in 11 adolescents. The C‐peptide minimal model was identified on C‐peptide and glucose data to quantify indices of β‐cell function: static φs and dynamic φd responsivity to glucose from which total responsivity φ was also measured. The glucose minimal model was identified on glucose and insulin data to estimate insulin sensitivity, SI, which was compared to a reference measure, SIref, provided by a tracer method. Disposition indices, which adjust insulin secretion for insulin action, were then calculated. Indices of β‐cell function were φs = 51.35 ± 8.89 × 10?9min?1, φd = 1,392 ± 258 × 10?9, and φ = 82.09 ± 17.70 × 10?9min?1. Insulin sensitivity was SI = 14.19 ± 2.73 × 10?4, not significantly different from SIref = 14.96 ± 3.04 × 10?4 dl/kg·min per µU/ml, and well correlated: r = 0.98, P < 0.0001, thus indicating that SI can be accurately measured from an oral test. Disposition indices were DIs = 1,040 ± 201 × 10?14 dl/kg/min2 per pmol/l, DId = 33,178 ± 10,720 × 10?14 dl/kg/min per pmol/l, DI = 1,844 ± 522 × 10?14 dl/kg/min2 per pmol/l. Virtually the same minimal model assessment was obtained with a reduced 3 h, 9‐sample protocol. OGTT interpreted with C‐peptide and glucose minimal model has the potential to provide novel insight regarding the regulation of glucose metabolism in adolescents, and to evaluate the effect of obesity and interventions such as diet and exercise. 相似文献
70.
Campos IT Silva MM Azzolini SS Souza AF Sampaio CA Fritz H Tanaka AS 《Archives of biochemistry and biophysics》2004,425(1):87-94
A small combinatorial library of LDTI mutants (5.2 x 10(4)) restricted to the P1-P4' positions of the reactive site was displayed on the pCANTAB 5E phagemid, and LDTI fusion phages were produced and selected for potent neutrophil elastase and plasmin inhibitors. Strong fusion phage binders were analyzed by ELISA on enzyme-coated microtiter plates and the positive phages had their DNA sequenced. The LDTI variants: 29E (K8A, I9A, L10F, and K11F) and 19E (K8A, K11Q, and P12Y) for elastase and 2Pl (K11W and P12N), 8Pl (I9V, K11W, and P12E), and 10Pl (I9T, K11L, and P12L) for plasmin were produced with a Saccharomyces cerevisiae expression system. New strong elastase and plasmin inhibitors were 29E and 2Pl, respectively. LDTI-29E was a potent and specific neutrophil elastase inhibitor K(i) =0.5 nM), affecting no other tested enzymes. LDTI-2Pl was the strongest plasmin inhibitor ( K(i) =1.7nM) in the LDTI mutant library. This approach allowed selection of new specific serine proteinase inhibitors for neutrophil elastase and plasmin (a thrombin inhibitor variant was previously described), from a unique template molecule, LDTI, a Kazal type one domain inhibitor, by only 2-4 amino acid replacements. Our data validate this small LDTI combinatorial library as a tool to generate specific serine proteinase inhibitors suitable for drug design and enzyme-inhibitor interaction studies. 相似文献