全文获取类型
收费全文 | 7436篇 |
免费 | 510篇 |
国内免费 | 2篇 |
专业分类
7948篇 |
出版年
2023年 | 42篇 |
2022年 | 92篇 |
2021年 | 159篇 |
2020年 | 84篇 |
2019年 | 128篇 |
2018年 | 147篇 |
2017年 | 136篇 |
2016年 | 235篇 |
2015年 | 349篇 |
2014年 | 395篇 |
2013年 | 508篇 |
2012年 | 578篇 |
2011年 | 571篇 |
2010年 | 404篇 |
2009年 | 309篇 |
2008年 | 437篇 |
2007年 | 430篇 |
2006年 | 455篇 |
2005年 | 387篇 |
2004年 | 387篇 |
2003年 | 345篇 |
2002年 | 325篇 |
2001年 | 74篇 |
2000年 | 47篇 |
1999年 | 70篇 |
1998年 | 73篇 |
1997年 | 81篇 |
1996年 | 59篇 |
1995年 | 36篇 |
1994年 | 47篇 |
1993年 | 39篇 |
1992年 | 32篇 |
1991年 | 31篇 |
1990年 | 27篇 |
1989年 | 28篇 |
1988年 | 27篇 |
1987年 | 21篇 |
1986年 | 22篇 |
1985年 | 30篇 |
1984年 | 29篇 |
1983年 | 24篇 |
1982年 | 35篇 |
1981年 | 29篇 |
1980年 | 25篇 |
1979年 | 17篇 |
1977年 | 16篇 |
1976年 | 12篇 |
1975年 | 12篇 |
1974年 | 11篇 |
1973年 | 18篇 |
排序方式: 共有7948条查询结果,搜索用时 0 毫秒
181.
Damiano Totaro Mario Rothbauer Matthias G. Steiger Torsten Mayr Hsiang-Yu Wang Yu-Sheng Lin Michael Sauer Martin Altvater Peter Ertl Diethard Mattanovich 《Biotechnology and bioengineering》2020,117(7):2046-2057
A key challenge for bioprocess engineering is the identification of the optimum process conditions for the production of biochemical and biopharmaceutical compounds using prokaryotic as well as eukaryotic cell factories. Shake flasks and bench-scale bioreactor systems are still the golden standard in the early stage of bioprocess development, though they are known to be expensive, time-consuming, and labor-intensive as well as lacking the throughput for efficient production optimizations. To bridge the technological gap between bioprocess optimization and upscaling, we have developed a microfluidic bioreactor array to reduce time and costs, and to increase throughput compared with traditional lab-scale culture strategies. We present a multifunctional microfluidic device containing 12 individual bioreactors (Vt = 15 µl) in a 26 mm × 76 mm area with in-line biosensing of dissolved oxygen and biomass concentration. Following initial device characterization, the bioreactor lab-on-a-chip was used in a proof-of-principle study to identify the most productive cell line for lactic acid production out of two engineered yeast strains, evaluating whether it could reduce the time needed for collecting meaningful data compared with shake flasks cultures. Results of the study showed significant difference in the strains' productivity within 3 hr of operation exhibiting a 4- to 6-fold higher lactic acid production, thus pointing at the potential of microfluidic technology as effective screening tool for fast and parallelizable industrial bioprocess development. 相似文献
182.
Olga De Castro Antonietta Di Maio José Armando Lozada García Danilo Piacenti Mario Vázquez-Torres Paolo De Luca 《Annals of botany》2013,112(3):589-602
Background and Aims
Recent research on the history of Platanus reveals that hybridization phenomena occurred in the central American species. This study has two goals: to help resolve the evolutive puzzle of central American Platanus, and to test the potential of real-time polymerase chain reaction (PCR) for detecting ancient hybridization.Methods
Sequencing of a uniparental plastid DNA marker [psbA-trnH(GUG) intergenic spacer] and qualitative and quantitative single nucleotide polymorphism (SNP) genotyping of biparental nuclear ribosomal DNA (nrDNA) markers [LEAFY intron 2 (LFY-i2) and internal transcribed spacer 2 (ITS2)] were used.Key Results
Based on the SNP genotyping results, several Platanus accessions show the presence of hybridization/introgression, including some accessions of P. rzedowskii and of P. mexicana var. interior and one of P. mexicana var. mexicana from Oaxaca (= P. oaxacana). Based on haplotype analyses of the psbA-trnH spacer, five haplotypes were detected. The most common of these is present in taxa belonging to P. orientalis, P. racemosa sensu lato, some accessions of P. occidentalis sensu stricto (s.s.) from Texas, P. occidentalis var. palmeri, P. mexicana s.s. and P. rzedowskii. This is highly relevant to genetic relationships with the haplotypes present in P. occidentalis s.s. and P. mexicana var. interior.Conclusions
Hybridization and introgression events between lineages ancestral to modern central and eastern North American Platanus species occurred. Plastid haplotypes and qualitative and quantitative SNP genotyping provide information critical for understanding the complex history of Mexican Platanus. Compared with the usual molecular techniques of sub-cloning, sequencing and genotyping, real-time PCR assay is a quick and sensitive technique for analysing complex evolutionary patterns. 相似文献183.
Aroldo Cupello Mario Di Braccio Elena Gatta Giancarlo Grossi Periklis Nikas Francesca Pellistri Mauro Robello 《Neurochemical research》2013,38(12):2453-2462
GABAA receptor mediated inhibition plays an important role in modulating the input/output dynamics of cerebellum. A characteristic of cerebellar GABAA receptors is the presence in cerebellar granule cells of subunits such as α6 and δ which give insensitivity to classical benzodiazepines. In fact, cerebellar GABAA receptors have generally been considered a poor model for testing drugs which potentially are active at the benzodiazepine site. In this overview we show how rat cerebellar granule cells in culture may be a useful model for studying new benzodiazepine site agonists. This is based on the pharmacological separation of diazepam-sensitive α1 β2/3 γ2 receptors from those which are diazepam-insensitive and contain the α6 subunit. This is achieved by utilizing furosemide/Zn2+ which block α6 containing and incomplete receptors. 相似文献
184.
Carmen García-Ibarbia Jesús Delgado-Calle Iñigo Casafont Javier Velasco Jana Arozamena María I. Pérez-Núñez María A. Alonso María T. Berciano Fernando Ortiz José L. Pérez-Castrillón Agustín F. Fernández Mario F. Fraga María T. Zarrabeitia José A. Riancho 《Gene》2013
We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic and epigenetic mechanisms involved. 相似文献
185.
Francisco Riquelme Jesús Alvarado-Ortega Mario Ramos-Arias Miguel Hernández Isabelle Le Dez Thomas A. Lee-Whiting 《Historical Biology》2013,25(4):415-427
A fossil millipede representative of the order Stemmiulida is described on the basis of a well-preserved adult female trapped in amber from the Miocene of Simojovel, Chiapas, south-eastern México. The fossil specimen is named as Parastemmiulus elektron, a new genus and species. As observed in extant stemmiulids, this fossil shows a reduced number of ocelli, the distal larger than the proximal, as well as a total of 46 trunk segments including 2 apodous segments in front of the telson. The head of this ancient stemmiulid has three ocelli and a Tömösváry organ, characteristics not reported before in Stemmiulida, requiring the diagnosis of the order to be emended.http://zoobank.org/urn:lsid:zoobank.org:pub:361400A8-37D4-421F-B4FD-A0AE63BE538C 相似文献
186.
Borja L. Holgado Laura Martínez-Muñoz Juan Antonio Sánchez-Alcañiz Pilar Lucas Vicente Pérez-García Gema Pérez José Miguel Rodríguez-Frade Marta Nieto Óscar Marín Yolanda R. Carrasco Ana C. Carrera Manuel Álvarez-Dolado Mario Mellado 《Molecular neurobiology》2013,48(1):217-231
The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110β in NPC, only p110β participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110β blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110β is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110β is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex. 相似文献
187.
188.
George E. Fox Quyen Tran Mario Rivas Victor Stepanov 《Journal of biomolecular structure & dynamics》2013,31(1)
The protein synthesis machinery largely evolved prior to the last common ancestor and hence its study can provide insight to early events in the origin of life, including the transition from the hypothetical RNA world to living systems as we know them. By utilizing information from primary sequences, atomic resolution structures, and functional properties of the various components, it is possible to identify timing relationships (Hsiao et al., 2009; Fox, 2010). Taken together, these timing events are used to develop a preliminary time line for major evolutionary events leading to the modern protein synthesis machinery. It has been argued that a key initial event was the hybridization of two or more RNAs that created the peptidyl transferase center, (PTC), of the ribosome (Agmon et al. 2005). The PTC, left side of figure, contains a characteristic cavity/pore that serves as the entrance to the exit tunnel and is thought to be essential to the catalysis (Fox et al., 2012). This cavity is distinct from typical RNA pores (right side of figure) in that the nitrogenous bases face towards the lumen of the pore and thus are available for hydrogen bonding interactions. In typical RNA pores, the bases carefully avoid the lumen region. In support of Agmon et al. 2005), it is argued that this key difference reflects the fact the pore was created by an early hybridization event rather than normal RNA folding. 相似文献
189.
Mario Ramírez Gabriel Guillén Sara I. Fuentes Luis P. Íñiguez Rosaura Aparicio‐Fabre David Zamorano‐Sánchez Sergio Encarnación‐Guevara Dario Panzeri Bianca Castiglioni Paola Cremonesi Francesco Strozzi Alessandra Stella Lourdes Girard Francesca Sparvoli Georgina Hernández 《Physiologia plantarum》2013,149(3):389-407
190.
Nikolai Petrovsky Maximilian Larena Venkatraman Siddharthan Natalie A. Prow Roy A. Hall Mario Lobigs John Morrey 《Journal of virology》2013,87(18):10324-10333
West Nile virus (WNV), currently the cause of a serious U.S. epidemic, is a mosquito-borne flavivirus and member of the Japanese encephalitis (JE) serocomplex. There is currently no approved human WNV vaccine, and treatment options remain limited, resulting in significant mortality and morbidity from human infection. Given the availability of approved human JE vaccines, this study asked whether the JE-ADVAX vaccine, which contains an inactivated cell culture JE virus antigen formulated with Advax delta inulin adjuvant, could provide heterologous protection against WNV infection in wild-type and β2-microglobulin-deficient (β2m−/−) murine models. Mice immunized twice or even once with JE-ADVAX were protected against lethal WNV challenge even when mice had low or absent serum cross-neutralizing WNV titers prior to challenge. Similarly, β2m−/− mice immunized with JE-ADVAX were protected against lethal WNV challenge in the absence of CD8+ T cells and prechallenge WNV antibody titers. Protection against WNV could be adoptively transferred to naive mice by memory B cells from JE-ADVAX-immunized animals. Hence, in addition to increasing serum cross-neutralizing antibody titers, JE-ADVAX induced a memory B-cell population able to provide heterologous protection against WNV challenge. Heterologous protection was reduced when JE vaccine antigen was administered alone without Advax, confirming the importance of the adjuvant to induction of cross-protective immunity. In the absence of an approved human WNV vaccine, JE-ADVAX could provide an alternative approach for control of a major human WNV epidemic. 相似文献