全文获取类型
收费全文 | 45503篇 |
免费 | 3580篇 |
国内免费 | 124篇 |
专业分类
49207篇 |
出版年
2022年 | 434篇 |
2021年 | 781篇 |
2020年 | 555篇 |
2019年 | 748篇 |
2018年 | 882篇 |
2017年 | 764篇 |
2016年 | 1161篇 |
2015年 | 1790篇 |
2014年 | 1919篇 |
2013年 | 2627篇 |
2012年 | 2948篇 |
2011年 | 2768篇 |
2010年 | 1944篇 |
2009年 | 1628篇 |
2008年 | 2201篇 |
2007年 | 2090篇 |
2006年 | 2009篇 |
2005年 | 1793篇 |
2004年 | 1752篇 |
2003年 | 1674篇 |
2002年 | 1652篇 |
2001年 | 1110篇 |
2000年 | 1024篇 |
1999年 | 916篇 |
1998年 | 498篇 |
1997年 | 521篇 |
1996年 | 427篇 |
1995年 | 406篇 |
1994年 | 337篇 |
1993年 | 378篇 |
1992年 | 637篇 |
1991年 | 587篇 |
1990年 | 550篇 |
1989年 | 494篇 |
1988年 | 400篇 |
1987年 | 395篇 |
1986年 | 381篇 |
1985年 | 438篇 |
1984年 | 399篇 |
1983年 | 360篇 |
1982年 | 280篇 |
1981年 | 295篇 |
1980年 | 254篇 |
1979年 | 324篇 |
1978年 | 284篇 |
1977年 | 304篇 |
1976年 | 271篇 |
1975年 | 285篇 |
1974年 | 274篇 |
1973年 | 267篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
92.
Duccio Malinverni Simone Marsili Alessandro Barducci Paolo De Los Rios 《PLoS computational biology》2015,11(6)
Hsp70s are a class of ubiquitous and highly conserved molecular chaperones playing a central role in the regulation of proteostasis in the cell. Hsp70s assist a myriad of cellular processes by binding unfolded or misfolded substrates during a complex biochemical cycle involving large-scale structural rearrangements. Here we show that an analysis of coevolution at the residue level fully captures the characteristic large-scale conformational transitions of this protein family, and predicts an evolutionary conserved–and thus functional–homo-dimeric arrangement. Furthermore, we highlight that the features encoding the Hsp70 dimer are more conserved in bacterial than in eukaryotic sequences, suggesting that the known Hsp70/Hsp110 hetero-dimer is a eukaryotic specialization built on a pre-existing template. 相似文献
93.
Marina Burgos-Silva Patricia Semedo-Kuriki Cassiano Donizetti-Oliveira Priscilla Barbosa Costa Marco Antonio Cenedeze Meire Ioshie Hiyane Alvaro Pacheco-Silva Niels Olsen Saraiva Camara 《PloS one》2015,10(11)
Acute and chronic kidney injuries (AKI and CKI) constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs) in an experimental model of nephrotoxicity induced by folic acid (FA) in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation. 相似文献
94.
During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed in the distal mesenchyme and regulated by Wnt signaling, acts on the distal epithelial progenitors to maintain them and prevent them from differentiating into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving epithelial cells secrete Wnt7b which then activates the PSMC niche to induce Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara stem cells to break quiescence, induce proliferation and initiate epithelial repair. Here we show that conditional deletion of the Wnt target gene c-Myc from the lung mesenchyme during development does not affect proper epithelial or mesenchymal differentiation. However, in the adult lung we show that after naphthalene-mediated airway epithelial injury c-Myc is important for the activation of the PSMC niche and as such induces proliferation and Fgf10 expression in PSMCs. Our data indicate that conditional deletion of c-Myc from PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells has no effect on airway epithelial regeneration. These findings may have important implications for understanding the misregulation of lung repair in asthma and COPD. 相似文献
95.
The plant-specific insert is an approximately 100-residue domain found exclusively within the C-terminal lobe of some plant aspartic proteases. Structurally, this domain is a member of the saposin-like protein family, and is involved in plant pathogen defense as well as vacuolar targeting of the parent protease molecule. Similar to other members of the saposin-like protein family, most notably saposins A and C, the recently resolved crystal structure of potato (Solanum tuberosum) plant-specific insert has been shown to exist in a substrate-bound open conformation in which the plant-specific insert oligomerizes to form homodimers. In addition to the open structure, a closed conformation also exists having the classic saposin fold of the saposin-like protein family as observed in the crystal structure of barley (Hordeum vulgare L.) plant-specific insert. In the present study, the mechanisms of tertiary and quaternary conformation changes of potato plant-specific insert were investigated in silico as a function of pH. Umbrella sampling and determination of the free energy change of dissociation of the plant-specific insert homodimer revealed that increasing the pH of the system to near physiological levels reduced the free energy barrier to dissociation. Furthermore, principal component analysis was used to characterize conformational changes at both acidic and neutral pH. The results indicated that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin fold and suggest a potential new structural motif among saposin-like proteins. To our knowledge, this acidified PSI structure presents the first example of an alternative saposin-fold motif for any member of the large and diverse SAPLIP family. 相似文献
96.
Felipe Silva de Andrade Thiago Ribeiro de Carvalho Lucas Borges Martins Ariovaldo Antonio Giaretta 《Studies on Neotropical Fauna and Environment》2017,52(2):157-167
In this study, we re-describe the advertisement and territorial calls of Boana pardalis, carry out an acoustic comparison between the studied species and the other congeners of the B. faber group, and report for the first time the tympanic amplexus for the studied species. The advertisement call of B. pardalis can be used to supplement its diagnosis in the B. faber group based on temporal call traits, e.g. emission rate and emission pattern, as well as the call envelope. 相似文献
97.
Summary The xylanolytic and cellulolytic activity fromCellulomanas were reduced by high O2 concentrations in continous culture as well as by an air flow passed trough the samples, suggesting an inhibition or inactivation of enzymes in such conditions. 相似文献
98.
The concept of the blood-aqueous barrier is largely based on the use of horseradish peroxidase (HRP). The present investigation
was designed to check its reliability as a macromolecular tracer, especially with regard to the transport of plasma proteins.
Rabbits were killed 5 min to 24 h after being intravenously injected with HRP. The tracer diffused rapidly, reaching the aqueous
humor of the eye in 3 min or less and was detected at high concentration in the narrow space between the outer epithelial
layer of the ciliary epithelium and the wall of the pervious capillaries in the stroma of the processes. HRP appeared to migrate
from the blood to the posterior chamber, permeating the tight junctions, viz., the anatomical basis of the blood-aqueous barrier.
It was detected at higher concentration at the anterior surface of the iris, at short time intervals; this was interpreted
as penetration of the tracer from the aqueous humor of the anterior chamber. The choroid was also labeled in continuation
with the reaction in the stroma of the pars plana of the ciliary body which, in turn, sometimes reached the iris root. Therefore,
the pervious blood vessels of the choroid could be a source of macromolecules for the iris root. HRP also induced the formation
of lysosomes in the ciliary epithelium. This can hardly be accepted as the way in which plasma proteins are physiologically
transported to the aqueous humor. However, the pathway of HRP migration over short time intervals seems to be in agreement
with previous research indicating that the entrance of serum albumin into the posterior chamber is the first step of its incorporation
into the aqueous humor.
Received: 7 June 1996 / Accepted: 15 January 1997 相似文献
99.
J. De Rudder J. Leclerc M Mercier G. Gosselin J. L. Imbach 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):221-223
Abstract D-Xylo and Lyxofuranonucleosides have not been extensively studied. Therefore in order to perform a systematic Structure-Antiviral Activity Relationship of the nucleoside analogs we have first synthesized their α and β anomers, some of them being unknown or their structure doubtful in the literature. 相似文献
100.
Laura Miralles Santiago Lens Antonio Rodríguez-Folgar Manuel Carrillo Vidal Martín Bjarni Mikkelsen Eva Garcia-Vazquez 《PloS one》2013,8(8)
Visual species identification of cetacean strandings is difficult, especially when dead specimens are degraded and/or species are morphologically similar. The two recognised pilot whale species (Globicephala melas and Globicephala macrorhynchus) are sympatric in the North Atlantic Ocean. These species are very similar in external appearance and their morphometric characteristics partially overlap; thus visual identification is not always reliable. Genetic species identification ensures correct identification of specimens. Here we have employed one mitochondrial (D-Loop region) and eight nuclear loci (microsatellites) as genetic markers to identify six stranded pilot whales found in Galicia (Northwest Spain), one of them of ambiguous phenotype. DNA analyses yielded positive amplification of all loci and enabled species identification. Nuclear microsatellite DNA genotypes revealed mixed ancestry for one individual, identified as a post-F1 interspecific hybrid employing two different Bayesian methods. From the mitochondrial sequence the maternal species was Globicephala melas. This is the first hybrid documented between Globicephala melas and G. macrorhynchus, and the first post-F1 hybrid genetically identified between cetaceans, revealing interspecific genetic introgression in marine mammals. We propose to add nuclear loci to genetic databases for cetacean species identification in order to detect hybrid individuals. 相似文献