全文获取类型
收费全文 | 2348篇 |
免费 | 275篇 |
专业分类
2623篇 |
出版年
2023年 | 10篇 |
2022年 | 24篇 |
2021年 | 41篇 |
2020年 | 36篇 |
2019年 | 43篇 |
2018年 | 60篇 |
2017年 | 43篇 |
2016年 | 80篇 |
2015年 | 105篇 |
2014年 | 131篇 |
2013年 | 121篇 |
2012年 | 178篇 |
2011年 | 137篇 |
2010年 | 104篇 |
2009年 | 91篇 |
2008年 | 107篇 |
2007年 | 101篇 |
2006年 | 114篇 |
2005年 | 87篇 |
2004年 | 73篇 |
2003年 | 88篇 |
2002年 | 73篇 |
2001年 | 75篇 |
2000年 | 66篇 |
1999年 | 51篇 |
1998年 | 30篇 |
1997年 | 28篇 |
1996年 | 44篇 |
1995年 | 23篇 |
1994年 | 32篇 |
1993年 | 22篇 |
1992年 | 46篇 |
1991年 | 35篇 |
1990年 | 35篇 |
1989年 | 29篇 |
1988年 | 27篇 |
1987年 | 29篇 |
1986年 | 25篇 |
1985年 | 21篇 |
1984年 | 22篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 11篇 |
1980年 | 15篇 |
1979年 | 10篇 |
1978年 | 9篇 |
1975年 | 7篇 |
1973年 | 7篇 |
1972年 | 7篇 |
1967年 | 7篇 |
排序方式: 共有2623条查询结果,搜索用时 15 毫秒
81.
Pérez D Crespo M Solé L Prat M Carcasona C Calama E Otal R Gavaldá A Gómez-Angelats M Miralpeix M Puig C 《Bioorganic & medicinal chemistry letters》2011,21(5):1545-1548
The synthesis of diverse functionalized ureas in a semi-parallel fashion is described, as well as their β1/β2-adrenergic activities and the corresponding structure-activity relationship (SAR). We have focused on lipophilicity and duration of action, and we have discovered a strong correlation in this series of molecules. A quantitative structure-activity relationship (QSAR) analysis will be presented that quantifies this relationship. 相似文献
82.
The ultrastructure of endoderm cells of the area pellucida has been analysed in the chick embryo by stereological methods. These cells show a specific subcellular evolution which can be correlated with several aspects of morphogenetic behaviour. The cell form coefficient (CFc) changes notably from stage 5 (0.683) to stage 8 (0.446) accompanying the transformation of this layer into a squamous epithelium. An increase of the nuclear surface density is observed and is discussed in relation to the control of nucleocytoplasmic interchange. The mitochondrial volume and surface densities remain constant (3.12% of cellular volume and 0.727 mitochondria/mu(3) respectively). The endodermal cells possess higher levels of vitelline reserves (lipid bodies, 6.97% and yolk droplets, 8.90%) than other cellular types of the chick embryo. This fact is discussed with respect to the role of the endoderm in the phagocytosis of yolk. The RER length density shows an increase that could be related to some specific changes of the extracellular matrix during this period, but this fact remains to be demonstrated in relation to changes of Golgi membranes. 相似文献
83.
The mechanical stability of ubiquitin is linkage dependent 总被引:12,自引:0,他引:12
Carrion-Vazquez M Li H Lu H Marszalek PE Oberhauser AF Fernandez JM 《Nature structural biology》2003,10(9):738-743
Ubiquitin chains are formed through the action of a set of enzymes that covalently link ubiquitin either through peptide bonds or through isopeptide bonds between their C terminus and any of four lysine residues. These naturally occurring polyproteins allow one to study the mechanical stability of a protein, when force is applied through different linkages. Here we used single-molecule force spectroscopy techniques to examine the mechanical stability of N-C-linked and Lys48-C-linked ubiquitin chains. We combined these experiments with steered molecular dynamics (SMD) simulations and found that the mechanical stability and unfolding pathway of ubiquitin strongly depend on the linkage through which the mechanical force is applied to the protein. Hence, a protein that is otherwise very stable may be easily unfolded by a relatively weak mechanical force applied through the right linkage. This may be a widespread mechanism in biological systems. 相似文献
84.
Fernandez E.; Maranon E.; Harbour D. S.; Kristiansen S.; Heimdal B. R. 《Journal of plankton research》1996,18(12):2349-2366
Blooms of the coccolithophorid Emiliania huxleyi were monitoredin two land-locked fjords, Fauskangerpollen and Nordåsvannet(Western Norway), in May 1993. The chemical composition of particulatematter, size-fractionated photosynthesis, calcification, nitrogenuptake rates and the patterns of macromolecular synthesis wereexamined during the peak and decline of E.huxleyi blooms. Thetemporal evolution of the bloom in Fauskangerpollen was definedby a gradual decrease in cell abundance and cell-specific calcificationrates, and by increasing numbers of empty coccospheres and theratio detached coccoliths/living cells. A large proportion ofthe nitrogen required for microplankton growth was suppliedby aminonium and dissolved organic compounds such as urea and,as a consequence, the f-ratios were low (0.2). In general, nitrogenuptake patterns were consistent with ambient concentrationsof nitrogenous species. The photosynthetic carbon metabolismof E.huxleyi dominated phytoplankton assemblages was characterizedby high carbon allocation into lipids and relatively low carbonincorporation into protein as compared with diatom-dominatedassemblages. Consequently, the organic C/nitrogen uptake ratiodetermined stoichiometrically was significantly higher (up to10.8) when coccolithophorids were dominant than in diatom-basedor mixed-phyto-plankton assemblages. These carbon incorporationpatterns were reflected in differences in the chemical compositionof particulate matter. 相似文献
85.
Maathuis F Verlin D Smith FA Sanders D Fernandez JA Walker NA 《Plant physiology》1996,112(4):1609-1616
Plant roots utilize at least two distinct pathways with high and low affinities to accumulate K+. The system for high-affinity K+ uptake, which takes place against the electrochemical K+ gradient, requires direct energization. Energization of K+ uptake via Na+ coupling has been observed in algae and was recently proposed as a mechanism for K+ uptake in wheat (Triticum aestivum L.). To investigate whether Na+ coupling has general physiological relevance in energizing K+ transport, we screened a number of species, including Arabidopsis thaliana L. Heynh. ecotype Columbia, wheat, and barley (Hordeum vulgare L.), for the presence of Na+-coupled K+ uptake. Rb+-flux analysis and electrophysiological K+-transport assays were performed in the presence and absence of Na+ and provided evidence for a coupling between K+ and Na+ transport in several aquatic species. However, all investigated terrestrial species were able to sustain growth and K+ uptake in the absence of Na+. Furthermore, the addition of Na+ was either without effect or inhibited K+ absorption. The latter characteristic was independent of growth conditions with respect to Na+ status and pH. Our results suggest that in terrestrial species Na+-coupled K+ transport has no or limited physiological relevance, whereas in certain aquatic angiosperms and algae this type of secondary transport energization plays a significant role. 相似文献
86.
Gray level Co‐occurrence Matrices (GLCM) to assess microstructural and textural changes in pre‐implantation embryos 下载免费PDF全文
87.
Mireia Herrando-Grabulosa Roger Mulet Albert Pujol José Manuel Mas Xavier Navarro Patrick Aloy Mireia Coma Caty Casas 《PloS one》2016,11(1)
Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology), we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis. 相似文献
88.
Eva del Amo Cristina Esteva Susanna Hernandez-Bou Carmen Galles Marian Navarro Goretti Sauca Alvaro Diaz Paula Gassiot Carmina Marti Nieves Larrosa Pilar Ciruela Mireia Jane Raquel Sá-Le?o Carmen Mu?oz-Almagro Catalan Study Group of Invasive Pneumococcal Disease 《PloS one》2016,11(3)
The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types—defined by MLST—were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p<0.01). This decrease was mainly attributable to serotypes 19A and 7F. Serotype 12F achieved the third position in 2013 (n = 22, 6.4%). The most frequent clonal types found were ST306 (n = 154, 9.9%), ST191 (n = 111, 7.2%), ST989 (n = 85, 5.5%) and ST180 (n = 80, 5.2%). Despite their decrease, PCV13 serotypes continue to be a major cause of disease in Spain. These results emphasize the need for complete PCV13 vaccination. 相似文献
89.
Michela Menegon Azucena Bardají Flor Martínez-Espinosa Camila B?tto-Menezes Maria Ome-Kaius Ivo Mueller Inoni Betuela Myriam Arévalo-Herrera Swati Kochar Sanjay K. Kochar Puneet Jaju Dhiraj Hans Chetan Chitnis Norma Padilla María Eugenia Castellanos Lucía Ortiz Sergi Sanz Mireia Piqueras Meghna Desai Alfredo Mayor Hernando del Portillo Clara Menéndez Carlo Severini 《PloS one》2016,11(3)
Plasmodium vivax is the most widely distributed human parasite and the main cause of human malaria outside the African continent. However, the knowledge about the genetic variability of P. vivax is limited when compared to the information available for P. falciparum. We present the results of a study aimed at characterizing the genetic structure of P. vivax populations obtained from pregnant women from different malaria endemic settings. Between June 2008 and October 2011 nearly 2000 pregnant women were recruited during routine antenatal care at each site and followed up until delivery. A capillary blood sample from the study participants was collected for genotyping at different time points. Seven P. vivax microsatellite markers were used for genotypic characterization on a total of 229 P. vivax isolates obtained from Brazil, Colombia, India and Papua New Guinea. In each population, the number of alleles per locus, the expected heterozygosity and the levels of multilocus linkage disequilibrium were assessed. The extent of genetic differentiation among populations was also estimated. Six microsatellite loci on 137 P. falciparum isolates from three countries were screened for comparison. The mean value of expected heterozygosity per country ranged from 0.839 to 0.874 for P. vivax and from 0.578 to 0.758 for P. falciparum. P. vivax populations were more diverse than those of P. falciparum. In some of the studied countries, the diversity of P. vivax population was very high compared to the respective level of endemicity. The level of inter-population differentiation was moderate to high in all P. vivax and P. falciparum populations studied. 相似文献
90.
Fernandez Ocaña M Jarvis J Parker R Bramley PM Halket JM Patel RK Neubert H 《Proteomics》2005,5(5):1209-1216
Protonated peptides derived from proline‐rich proteins (PRP) are often difficult to sequence by standard collision‐induced dissociation (CID) mass spectrometry (MS) due to preferential amide bond cleavage N‐terminal to proline. In connection with bovine spongiform encephalopathy regulations, proteolytic products derived from the PRP collagen have been suggested as markers for contamination of animal feedstuffs with processed animal protein (Fernandez Ocaña, M. et al., Analyst 2004, 129, 111–115). Herein, we report the identification of these marker peptides using the strategy of C‐terminal sequencing by CID MS from their sodium and lithium adducts. Upon fragmentation a new cationized peptide was produced that is one C‐terminal amino acid shorter in length. This dissociation pathway allowed for the facile identification of the C‐terminal residue by matrix‐assisted laser desorption/ionization tandem time‐of‐flight mass spectrometry. Each newly formed cationized peptide was further fragmented by up to seven stages of electrospray ionization ion trap MS. Proline‐rich C‐terminal sequence tags were established which permitted successful database identification of collagen alpha type I proteins. 相似文献