全文获取类型
收费全文 | 4123篇 |
免费 | 315篇 |
国内免费 | 1篇 |
出版年
2023年 | 8篇 |
2022年 | 35篇 |
2021年 | 70篇 |
2020年 | 41篇 |
2019年 | 51篇 |
2018年 | 87篇 |
2017年 | 59篇 |
2016年 | 124篇 |
2015年 | 217篇 |
2014年 | 225篇 |
2013年 | 288篇 |
2012年 | 387篇 |
2011年 | 376篇 |
2010年 | 194篇 |
2009年 | 171篇 |
2008年 | 267篇 |
2007年 | 285篇 |
2006年 | 237篇 |
2005年 | 247篇 |
2004年 | 209篇 |
2003年 | 187篇 |
2002年 | 187篇 |
2001年 | 43篇 |
2000年 | 32篇 |
1999年 | 47篇 |
1998年 | 44篇 |
1997年 | 47篇 |
1996年 | 40篇 |
1995年 | 25篇 |
1994年 | 27篇 |
1993年 | 18篇 |
1992年 | 21篇 |
1991年 | 18篇 |
1990年 | 16篇 |
1989年 | 13篇 |
1988年 | 13篇 |
1987年 | 11篇 |
1986年 | 19篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1978年 | 5篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有4439条查询结果,搜索用时 15 毫秒
91.
92.
Anne Thoustrup Saber Jacob Stuart Lamson Nicklas Raun Jacobsen Gitte Ravn-Haren Karin S?rig Hougaard Allen Njimeri Nyendi Pia Wahlberg Anne Mette Madsen Petra Jackson H?kan Wallin Ulla Vogel 《PloS one》2013,8(7)
Background
Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk.Methods
We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes.Results
Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points.Conclusions
Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease. 相似文献93.
Jin Young K. Kininmonth Stuart Lundgren Petra B. van Oppen Madeleine J. H. Willis Bette L. 《Coral reefs (Online)》2020,39(1):147-158
Coral Reefs - In the face of unprecedented rates of environmental alterations, the necessity to predict the capacity of corals to respond adaptively in a complex ecological system is becoming... 相似文献
94.
Zoltán Máté Marietta Zita Poles Gábor Szabó Mária Bagyánszki Petra Talapka Éva Fekete Nikolett Bódi 《Cell and tissue research》2013,352(2):199-206
Cholecystokinin (CCK) is an early marker of both neuronal and endocrine cell lineages in the developing gastrointestinal tract. To determine the quantitative properties and the spatial distribution of the CCK-expressing myenteric neurones in early postnatal life, a transgenic mouse strain with a CCK promoter-driven red fluorescent protein (DsRedT3/CCK) was established. The cell-specific expression of DsRedT3/CCK was validated by in situ hybridization with a CCK antisense riboprobe and by in situ hybridization coupled with immunohistochemistry involving a monoclonal antibody to CCK. A gradual increase in the DsRedT3/CCK-expressing enteric neurones with clear regional differences was documented from birth until the suckling to weaning transition, in parallel with the period of rapid intestinal growth and functional maturation. To evaluate the proportion of myenteric neurones in which DsRedT3/CCK transgene expression was colocalized with the enteric neuronal marker peripherin, immunofluorescence techniques were applied. All DsRedT3/CCK neurones were peripherin-immunoreactive and the proportion of DsRedT3/CCK-expressing myenteric neurones in the duodenum was the highest after the third week of life, when the number of peripherin-immunoreactive myenteric neurones in this region had decreased. Nearly all of the DsRedT3/CCK-expressing neurones also expressed 5-hydroxytryptophan (5-HT). Thus, by utilizing a new transgenic mouse strain, we have demonstrated a small number of CCK-expressing myenteric neurones with a developmentally regulated spatiotemporal distribution. The coexistence of CCK and 5-HT in the majority of these neurones suggests their possible regulatory role in feeding at the suckling to weaning transition. 相似文献
95.
96.
?sa Segerstolpe Sander Granneman Petra Bj?rk Flavia de Lima Alves Juri Rappsilber Charlotta Andersson Martin H?gbom David Tollervey Lars Wieslander 《Nucleic acids research》2013,41(2):1178-1190
Ribosomal subunit biogenesis in eukaryotes is a complex multistep process. Mrd1 is an essential and conserved small (40S) ribosomal subunit synthesis factor that is required for early cleavages in the 35S pre-ribosomal RNA (rRNA). Yeast Mrd1 contains five RNA-binding domains (RBDs), all of which are necessary for optimal function of the protein. Proteomic data showed that Mrd1 is part of the early pre-ribosomal complexes, and deletion of individual RBDs perturbs the pre-ribosomal structure. In vivo ultraviolet cross-linking showed that Mrd1 binds to the pre-rRNA at two sites within the 18S region, in helix 27 (h27) and helix 28. The major binding site lies in h27, and mutational analyses shows that this interaction requires the RBD1-3 region of Mrd1. RBD2 plays the dominant role in h27 binding, but other RBDs also contribute directly. h27 and helix 28 are located close to the sequences that form the central pseudoknot, a key structural feature of the mature 40S subunit. We speculate that the modular structure of Mrd1 coordinates pseudoknot formation with pre-rRNA processing and subunit assembly. 相似文献
97.
98.
Petra Mackeldanz Jürgen Alves Elisabeth Möncke-Buchner Karol H. Wyszomirski Detlev H. Krüger Monika Reuter 《Biochimie》2013
For efficient DNA hydrolysis, Type III restriction endonuclease EcoP15I interacts with two inversely oriented recognition sites in an ATP-dependent process. EcoP15I consists of two methylation (Mod) subunits and a single restriction (Res) subunit yielding a multifunctional enzyme complex able to methylate or to hydrolyse DNA. Comprehensive sequence alignments, limited proteolysis and mass spectroscopy suggested that the Res subunit is a fusion of a motor or translocase (Tr) domain of superfamily II helicases and an endonuclease domain with a catalytic PD…EXK motif. In the Tr domain, seven predicted helicase motifs (I, Ia, II–VI), a recently discovered Q-tip motif and three additional regions (IIIa, IVa, Va) conserved among Type III restriction enzymes have been identified that are predicted to be involved in DNA binding and ATP hydrolysis. Because DNA unwinding activity for EcoP15I (as for bona fide helicases) has never been found and EcoP15I ATPase rates are only low, the functional importance of the helicase motifs and regions was questionable and has never been probed systematically. Therefore, we mutated all helicase motifs and conserved regions predicted in Type III restriction enzyme EcoP15I and examined the functional consequences on EcoP15I enzyme activity and the structural integrity of the variants by CD spectroscopy. The resulting eleven enzyme variants all, except variant IVa, are properly folded showing the same secondary structure distribution as the wild-type enzyme. Classical helicase motifs I–VI are important for ATP and DNA cleavage by EcoP15I and mutations therein led to complete loss of ATPase and cleavage activity. Among the catalytically inactive enzyme variants three preserved the ability to bind ATP. In contrast, newly assigned motifs Q-tip, Ia and Va are not essential for EcoP15I activity and the corresponding enzyme variants were still catalytically active. DNA binding was only marginally reduced (2–7 fold) in all enzyme variants tested. 相似文献
99.
100.
Peter M. Bowers Tamlyn Y. Neben Geoffery L. Tomlinson Jennifer L. Dalton Larry Altobell Xue Zhang John L. Macomber Betty F. Wu Rachelle M. Toobian Audrey D. McConnell Petra Verdino Betty Chau Robert A. Horlick David J. King 《The Journal of biological chemistry》2013,288(11):7688-7696
A method for simultaneous humanization and affinity maturation of monoclonal antibodies has been developed using heavy chain complementarity-determining region (CDR) 3 grafting combined with somatic hypermutation in vitro. To minimize the amount of murine antibody-derived antibody sequence used during humanization, only the CDR3 region from a murine antibody that recognizes the cytokine hβNGF was grafted into a nonhomologous human germ line V region. The resulting CDR3-grafted HC was paired with a CDR-grafted light chain, displayed on the surface of HEK293 cells, and matured using in vitro somatic hypermutation. A high affinity humanized antibody was derived that was considerably more potent than the parental antibody, possessed a low pm dissociation constant, and demonstrated potent inhibition of hβNGF activity in vitro. The resulting antibody contained half the heavy chain murine donor sequence compared with the same antibody humanized using traditional methods. 相似文献