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71.
72.
RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity 总被引:2,自引:0,他引:2 下载免费PDF全文
Jenkins D Seelow D Jehee FS Perlyn CA Alonso LG Bueno DF Donnai D Josifova D Josifiova D Mathijssen IM Morton JE Orstavik KH Sweeney E Wall SA Marsh JL Nurnberg P Passos-Bueno MR Wilkie AO 《American journal of human genetics》2007,80(6):1162-1170
Carpenter syndrome is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we found linkage to chromosome 6p12.1-q12 and, in 15 independent families, identified five different mutations (four truncating and one missense) in RAB23, which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. In 10 patients, the disease was caused by homozygosity for the same nonsense mutation, L145X, that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Surprisingly, nonsense mutations of Rab23 in open brain mice cause recessive embryonic lethality with neural-tube defects, suggesting a species difference in the requirement for RAB23 during early development. The discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranial-suture biogenesis--an unexpected finding, given that craniosynostosis is not usually associated with mutations of other HH-pathway components--and provides a new molecular target for studies of obesity. 相似文献
73.
Sandro Cavicchi Daniela Guerra Vanna Natali Cristina Pezzoli Gianfranco Giorgi 《Journal of evolutionary biology》1989,2(4):235-251
From a laboratory stock of Drosophila melanogaster (Oregon), reared for more than 20 years at 18° C, a new population was derived and maintained at 28° C for 8 years. The chromosomal and cytoplasmic contribution to genetic divergence between the two populations was estimated. Six body traits and reproductive fitness were taken into account. The third chromosome is responsible for the adaptive difference for temperature between the two lines. Temperature-selected genes which control body size are located on the second and third chromosomes, although the contribution of each chromosome depends on the environment in which the flies develop. The correlation between the chromosomal and cytoplasmic contributions to different traits and fitness, changes with temperature. At 28° C the correlation between fitness and each body trait is proportional to the response to selection exhibited by each of them, but this is not true at 18° C. Body size has, therefore, an adaptive significance in relation to temperature, which is expressed only in the environment where selection occurs. Cytoplasmic genes affect almost all characters to an extent similar to that of chromosomal genes. Inter-chromosomal and nucleo-cytoplasmic interactions are present and also change with temperature. In general, genes selected in a given environment produce greater phenotypic changes in that environment than in another. The population that experienced both temperatures is fitter in both environments, suggesting that the capacity to adapt to warm temperatures depends on genes other than those which are involved in the adaptation to cold. 相似文献
74.
Schwabe TM Gloddek K Schluesener D Kruip J 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,786(1-2):45-59
The gene products Ycf3 (hypothetical chloroplast open reading frame) and BtpA (biogenesis of thylakoid protein) are thought to be involved in the biogenesis of the membrane protein complex photosystem I (PSI) from Synechocystis PCC 6803. PSI consists of 12 different subunits and binds more than 100 cofactors, making it a model protein to study different aspects of membrane protein biogenesis. For a detailed biophysical characterization of Ycf3 and BtpA pure proteins must be available in sufficient quantities. Therefore we cloned the corresponding genes into expression vectors. To facilitate purification we created His-tagged versions of Ycf3 and BtpA in addition to the unmodified forms. Immobilized metal affinity chromatography (IMAC) yielded His-tagged proteins which were used for the production of antibodies. Purification strategies for non-tagged proteins could also be established: Ycf3 could be purified in soluble form using a two-step purification in which ammonium sulfate precipitation was combined with anion-exchange chromatography (IEC). BtpA had to be purified from inclusion bodies by two-consecutive IEC steps under denaturing conditions. An optimized refolding protocol was established that yielded pure BtpA. In all cases, MALDI-TOF peptide mass fingerprinting (PMF) was used to confirm protein identity. Initially, size exclusion chromatography and CD-spectroscopy were used for biophysical characterization of the proteins. Both Ycf3 and BtpA show homo-oligomerization in vitro. In summary, purification protocols for Ycf3 and BtpA have been designed that yield pure proteins which can be used to probe the molecular function of these proteins for membrane protein biogenesis. 相似文献
75.
Effect of Bafilomycin A1 and Nocodazole on Endocytic Transport in HeLa Cells: Implications for Viral Uncoating and Infection 总被引:6,自引:11,他引:6 下载免费PDF全文
Nora Bayer Daniela Schober Elisabeth Prchla Robert F. Murphy Dieter Blaas Renate Fuchs 《Journal of virology》1998,72(12):9645-9655
Bafilomycin A1 (baf), a specific inhibitor of vacuolar proton ATPases, is commonly employed to demonstrate the requirement of low endosomal pH for viral uncoating. However, in certain cell types baf also affects the transport of endocytosed material from early to late endocytic compartments. To characterize the endocytic route in HeLa cells that are frequently used to study early events in viral infection, we used 35S-labeled human rhinovirus serotype 2 (HRV2) together with various fluid-phase markers. These virions are taken up via receptor-mediated endocytosis and undergo a conformational change to C-antigenic particles at a pH of <5.6, resulting in release of the genomic RNA and ultimately in infection (E. Prchla, E. Kuechler, D. Blaas, and R. Fuchs, J. Virol. 68:3713–3723, 1994). As revealed by fluorescence microscopy and subcellular fractionation of microsomes by free-flow electrophoresis (FFE), baf arrests the transport of all markers in early endosomes. In contrast, the microtubule-disrupting agent nocodazole was found to inhibit transport by accumulating marker in endosomal carrier vesicles (ECV), a compartment intermediate between early and late endosomes. Accordingly, lysosomal degradation of HRV2 was suppressed, whereas its conformational change and infectivity remained unaffected by this drug. Analysis of the subcellular distribution of HRV2 and fluid-phase markers in the presence of nocodazole by FFE revealed no difference from the control incubation in the absence of nocodazole. ECV and late endosomes thus have identical electrophoretic mobilities, and intraluminal pHs of <5.6 and allow uncoating of HRV2. As bafilomycin not only dissipates the low endosomal pH but also blocks transport from early to late endosomes in HeLa cells, its inhibitory effect on viral infection could in part also be attributed to trapping of virus in early endosomes which might lack components essential for uncoating. Consequently, inhibition of viral uncoating by bafilomycin cannot be taken to indicate a low pH requirement only. 相似文献
76.
Daniela Bustos‐Korts Ian K. Dawson Joanne Russell Alessandro Tondelli Davide Guerra Chiara Ferrandi Francesco Strozzi Ezequiel L. Nicolazzi Marta Molnar‐Lang Hakan Ozkan Maria Megyeri Peter Miko Esra akr Enes Yakr Noemi Trabanco Stefano Delbono Stylianos Kyriakidis Allan Booth Davide Cammarano Martin Mascher Peter Werner Luigi Cattivelli Laura Rossini Nils Stein Benjamin Kilian Robbie Waugh Fred A. van Eeuwijk 《The Plant journal : for cell and molecular biology》2019,99(6):1172-1191
Broadening the genetic base of crops is crucial for developing varieties to respond to global agricultural challenges such as climate change. Here, we analysed a diverse panel of 371 domesticated lines of the model crop barley to explore the genetics of crop adaptation. We first collected exome sequence data and phenotypes of key life history traits from contrasting multi‐environment common garden trials. Then we applied refined statistical methods, including some based on exomic haplotype states, for genotype‐by‐environment (G×E) modelling. Sub‐populations defined from exomic profiles were coincident with barley's biology, geography and history, and explained a high proportion of trial phenotypic variance. Clear G×E interactions indicated adaptation profiles that varied for landraces and cultivars. Exploration of circadian clock‐related genes, associated with the environmentally adaptive days to heading trait (crucial for the crop's spread from the Fertile Crescent), illustrated complexities in G×E effect directions, and the importance of latitudinally based genic context in the expression of large‐effect alleles. Our analysis supports a gene‐level scientific understanding of crop adaption and leads to practical opportunities for crop improvement, allowing the prioritisation of genomic regions and particular sets of lines for breeding efforts seeking to cope with climate change and other stresses. 相似文献
77.
Giovanni Bacci Patrizia Paganin Loredana Lopez Chiara Vanni Claudia Dalmastri Cristina Cantale Loretta Daddiego Gaetano Perrotta Daniela Dolce Patrizia Morelli Vanessa Tuccio Alessandra De Alessandri Ersilia Vita Fiscarelli Giovanni Taccetti Vincenzina Lucidi Annamaria Bevivino Alessio Mengoni 《PloS one》2016,11(6)
Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF. 相似文献
78.
Summary Conformational preferences of secretin as a model peptide have been analyzed by CD and IR spectroscopy in reverse micelles of AOT/isooctane/water and compared to those in aqueous TFE, in SDS micelles and in DMPG vesicles. Among the systems examined, reverse micelles and phospholipid vesicles displayed almost identical conformational equilibria. Very high lipid-to-peptide ratios can be obtained in reverse micelles with full retention of optical transparency, even at millimolar peptide concentrations, thus indicating this system to be an interesting mimic of cell membrane environments for spectroscopic analysis of bioactive peptide conformations.Abbreviations TFE
trifluoroethanol
- SDS
sodium dodecyl sulfate
- DMPG
dimyristoylphosphatidylglycerol
- AOT
bis(2-ethylhexyl)sulfosuccinate
- CMC
critical micellar concentration
- VIP
vasoactive intestinal peptide 相似文献
79.
Mauro Musto Daniele Cardinale Pietro Lucia Daniela Faraone 《Journal of applied animal welfare science : JAAWS》2016,19(3):217-233
This study evaluated whether showing a video of the different ways of raising goats for milk affected consumer acceptability. Four combinations, 2 Videos (intensive [INT] and semiextensive [SEM] system) × 2 Milk Types (semiskimmed [S] and whole [W] milk), were evaluated by 70 habitual consumers of goat milk, who scored their liking and purchase intention during blind (B), expected (E), and informed (I) acceptability sessions. In the B session, consumers tasted both milk types without information. S samples were preferred over W samples. In the E session, SEM video created high expectations in terms of milk liking and purchase intent, whereas the opposite happened when showing INT video. In the I session, consumers showed a clear preference for combinations created using SEM video, regardless of milk type. W-SEM and S-INT were worse (negative disconfirmation) and better (positive disconfirmation) than expected, respectively. A complete assimilation toward expectations occurred only for S-INT. INT video adversely affected the acceptability of S samples. Concerning purchase intent, W-SEM and S-SEM were worse than expected, but the assimilation was complete only for S-SEM: SEM video increased purchase intent for S samples. 相似文献
80.
Mela F Fritsche K Boersma H van Elsas JD Bartels D Meyer F de Boer W van Veen JA Leveau JH 《FEMS microbiology ecology》2008,66(1):45-62
Plasmid pTer331 from the bacterium Collimonas fungivorans Ter331 is a new member of the pIPO2/pSB102 family of environmental plasmids. The 40 457-bp sequence of pTer331 codes for 44 putative ORFs, most of which represent genes involved in replication, partitioning and transfer of the plasmid. We confirmed that pTer331 is stably maintained in its native host. Deletion analysis identified a mini-replicon capable of replicating autonomously in Escherichia coli and Pseudomonas putida. Furthermore, plasmid pTer331 was able to mobilize and retromobilize IncQ plasmid pSM1890 at typical rates of 10(-4) and 10(-8), respectively. Analysis of the 91% DNA sequence identity between pTer331 and pIPO2 revealed functional conservation of coding sequences, the deletion of DNA fragments flanked by short direct repeats (DR), and sequence preservation of long DRs. In addition, we experimentally established that pTer331 has no obvious contribution in several of the phenotypes that are characteristic of its host C. fungivorans Ter331, including the ability to efficiently colonize plant roots. Based on our findings, we hypothesize that cryptic plasmids such as pTer331 and pIPO2 might not confer an individual advantage to bacteria, but, due to their broad-host-range and ability to retromobilize, benefit bacterial populations by accelerating the intracommunal dissemination of the mobile gene pool. 相似文献