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961.
Martina Di Muzio Sabrina Wildner Sara Huber Michael Hauser Eva Vejvar Werner Auzinger Christof Regl Josef Laimer Danila Zennaro Nicole Wopfer Christian G. Huber Ronald van Ree Adriano Mari Peter Lackner Fatima Ferreira Mario Schubert Gabriele Gadermaier 《The Journal of biological chemistry》2020,295(51):17398
Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far. To reveal human IgE-binding regions of Art v 3, we produced three murine high-affinity mAbs, which showed 70–90% coverage of the allergenic epitopes from mugwort pollen–allergic patients. As reliable methods to determine structural epitopes with tightly interacting intact antibodies under native conditions are lacking, we developed a straightforward NMR approach termed hydrogen/deuterium exchange memory (HDXMEM). It relies on the slow exchange between the invisible antigen-mAb complex and the free 15N-labeled antigen whose 1H-15N correlations are detected. Due to a memory effect, changes of NH protection during antibody binding are measured. Differences in H/D exchange rates and analyses of mAb reactivity to homologous LTPs revealed three structural epitopes: two partially cross-reactive regions around α-helices 2 and 4 as well as a novel Art v 3–specific epitope at the C terminus. Protein variants with exchanged epitope residues confirmed the antibody-binding sites and revealed strongly reduced IgE reactivity. Using the novel HDXMEM for NMR epitope mapping allowed identification of the first structural epitopes of an allergenic pollen LTP. This knowledge enables improved cross-reactivity prediction for patients suffering from LTP allergy and facilitates design of therapeutics. 相似文献
962.
Mercy Okeyo Sabrina Hepner Robert E. Rollins Christina Hartberger Reinhard K. Straubinger Durdica Marosevic Stephanie A. Bannister Antra Bormane Michael Donaghy Andreas Sing Volker Fingerle Gabriele Margos 《Environmental microbiology》2020,22(12):5033-5047
Members of the Borrelia burgdorferi sensu lato (s.l.) species complex are known to cause human Lyme borreliosis. Because of longevity of some reservoir hosts and the Ixodes tick vectors' life cycle, long-term studies are required to better understand species and population dynamics of these bacteria in their natural habitats. Ticks were collected between 1999 and 2010 in three ecologically different habitats in Latvia. We used multilocus sequence typing utilizing eight chromosomally located housekeeping genes to obtain information about species and population fluctuations and/or stability of B. burgdorferi s.l. in these habitats. The average prevalence over all years was 18.9%. From initial high-infection prevalences of 25.5%, 33.1% and 31.8%, from 2002 onwards the infection rates steadily decreased to 7.3%. Borrelia afzelii and Borrelia garinii were the most commonly found genospecies but striking local differences were obvious. In one habitat, a significant shift from rodent-associated to bird-associated Borrelia species was noted whilst in the other habitats, Borrelia species composition was relatively stable over time. Sequence types (STs) showed a random spatial and temporal distribution. These results demonstrated that there are temporal regional changes and extrapolations from one habitat to the next are not possible. 相似文献
963.
Yanjiao Ma Yuan Ma Gabriele Giuli Holger Euchner Axel Groß Giovanni Orazio Lepore Francesco d'Acapito Dorin Geiger Johannes Biskupek Ute Kaiser Hanno M. Schütz Anna Carlsson Thomas Diemant Rolf Jürgen Behm Matthias Kuenzel Stefano Passerini Dominic Bresser 《Liver Transplantation》2020,10(25)
The development of alternative anode materials with higher volumetric and gravimetric capacity allowing for fast delithiation and, even more important, lithiation is crucial for next‐generation lithium‐ion batteries. Herein, the development of a completely new active material is reported, which follows an insertion‐type lithiation mechanism, metal‐doped CeO2. Remarkably, the introduction of carefully selected dopants, herein exemplified for iron, results in an increase of the achievable capacity by more than 200%, originating from the reduction of the dopant to the metallic state and additional space for the lithium ion insertion due to a significant off‐centering of the dopant atoms in the crystal structure, away from the original Ce site. In addition to the outstanding performance of such materials in high‐power lithium‐ion full‐cells, the selective reduction of the iron dopant under preservation of the crystal structure of the host material is expected to open up a new field of research. 相似文献
964.
965.
MUC1* Ligand,NM23-H1, Is a Novel Growth Factor That Maintains Human Stem Cells in a More Na?ve State
Benoit J. Smagghe Andrew K. Stewart Mark G. Carter Laura M. Shelton Kyle J. Bernier Eric J. Hartman Amy K. Calhoun Vasilios M. Hatziioannou Gabriele Lillacci Brian A. Kirk Brian A. DiNardo Kenneth S. Kosik Cynthia Bamdad 《PloS one》2013,8(3)
We report that a single growth factor, NM23-H1, enables serial passaging of both human ES and iPS cells in the absence of feeder cells, their conditioned media or bFGF in a fully defined xeno-free media on a novel defined, xeno-free surface. Stem cells cultured in this system show a gene expression pattern indicative of a more “naïve” state than stem cells grown in bFGF-based media. NM23-H1 and MUC1* growth factor receptor cooperate to control stem cell self-replication. By manipulating the multimerization state of NM23-H1, we override the stem cell''s inherent programming that turns off pluripotency and trick the cells into continuously replicating as pluripotent stem cells. Dimeric NM23-H1 binds to and dimerizes the extra cellular domain of the MUC1* transmembrane receptor which stimulates growth and promotes pluripotency. Inhibition of the NM23-H1/MUC1* interaction accelerates differentiation and causes a spike in miR-145 expression which signals a cell''s exit from pluripotency. 相似文献
966.
Chiara Nicolò Gabriele Di Sante Annabella Procoli Giuseppe Migliara Alessia Piermattei Mariagrazia Valentini Giovanni Delogu Achille Cittadini Gabriela Constantin Francesco Ria 《PloS one》2013,8(2)
DC deliver information regulating trafficking of effector T cells along T-cell priming. However, the role of pathogen-derived motives in the regulation of movement of T cells has not been studied. We hereinafter report that amount of M tuberculosis in the adjuvant modulates relocation of PLP139-151 specific T cells. In the presence of a low dose of M tuberculosis in the adjuvant, T cells (detected by CDR3 BV-BJ spectratyping, the so-called “immunoscope”) mostly reach the spleen by day 28 after immunization (“late relocation”) in the SJL strain, whereas T cells reach the spleen by d 14 with a high dose of M tuberculosis (“early relocation”). The C57Bl/6 background confers a dominant “early relocation” phenotype to F1 (SJL×C57Bl/6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 is responsible for “early/late” relocation phenotype. Egress of T lymphocytes is regulated by TLR2 expressed on T cells. Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand. 相似文献
967.
Nelly Mezzaroba Sonia Zorzet Erika Secco Stefania Biffi Claudio Tripodo Marco Calvaruso Ramiro Mendoza-Maldonado Sara Capolla Marilena Granzotto Ruben Spretz Gustavo Larsen Sandra Noriega Marianna Lucafò Eduardo Mansilla Chiara Garrovo Gustavo H. Marín Gabriele Baj Valter Gattei Gabriele Pozzato Luis Nú?ez Paolo Macor 《PloS one》2013,8(9)
968.
Coraline Bichet Renaud Scheifler Micha?l C?urdassier Romain Julliard Gabriele Sorci Claire Loiseau 《PloS one》2013,8(1)
Anthropogenic pollution poses a threat for the environment and wildlife. Trace metals (TMs) are known to have negative effects on haematological status, oxidative balance, and reproductive success in birds. These pollutants particularly increase in concentration in industrialized, urbanized and intensive agricultural areas. Pollutants can also interfere with the normal functioning of the immune system and, as such, alter the dynamics of host-parasite interactions. Nevertheless, the impact of pollution on infectious diseases has been largely neglected in natural populations of vertebrates. Here, we used a large spatial scale monitoring of 16 house sparrow (Passer domesticus) populations to identify environmental variables likely to explain variation in TMs (lead, cadmium, zinc) concentrations in the feathers. In five of these populations, we also studied the potential link between TMs, prevalence of infection with one species of avian malaria, Plasmodium relictum, and body condition. Our results show that lead concentration is associated with heavily urbanized habitats and that areas with large woodland coverage have higher cadmium and zinc feather concentrations. Our results suggest that lead concentration in the feathers positively correlates with P. relictum prevalence, and that a complex relationship links TM concentrations, infection status, and body condition. This is one of the first studies showing that environmental pollutants are associated with prevalence of an infectious disease in wildlife. The mechanisms underlying this effect are still unknown even though it is tempting to suggest that lead could interfere with the normal functioning of the immune system, as shown in other species. We suggest that more effort should be devoted to elucidate the link between pollution and the dynamics of infectious diseases. 相似文献
969.
Simona Cammarota Lucio Marcello Falconio Dario Bruzzese Alberico Luigi Catapano Manuela Casula Anna Citarella Luigi De Luca Maria Elena Flacco Lamberto Manzoli Maria Masulli Enrica Menditto Andrea Mezzetti Salvatore Riegler Ettore Novellino Gabriele Riccardi 《PloS one》2013,8(11)
Background
Few studies are available evaluating the impact of rapid-acting insulin analogues on long-term diabetes outcomes. Our aim was to compare the use of rapid-acting insulin analogues versus human regular insulin in relation to the occurrence of diabetic complications in a cohort of diabetic patients through the analysis of administrative databases.Methods
A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients free of macrovascular disease at baseline and treated either with human regular insulin or rapid-acting insulin analogues were followed for a maximum of 3 years. The incidence of diabetic complications was ascertained by hospital discharge claims. Hazard ratios (HRs) and 95% CIs of any diabetic complication and macrovascular, microvascular and metabolic complications were estimated separately using Cox proportional hazard models adjusted for patients’ characteristics and anti-diabetic drug use. Propensity score matching was also used to adjust for significant difference in the baseline characteristics between the two treatment groups.Results
A total of 2,286 patients were included: 914 receiving human regular insulin and 1,372 rapid-acting insulin analogues. During the follow-up, 286 (31.3%) incident events occurred in the human regular insulin group and 235 (17.1%) in the rapid-acting insulin analogue group. After propensity score-based matched-pair analyses, rapid-acting insulin analogues users had a HR of 0.73 (0.58–0.92) for any diabetes-related complication and HRs of 0.73 (0.55–0.93) and 0.55 (0.32–0.96) for macrovascular and metabolic complications respectively, as compared with human regular insulin users. No difference between the two groups was found for microvascular complications.Conclusions
Our findings suggest that the use of rapid-acting insulin analogues is associated with a lower risk of cardiovascular and metabolic complications compared with human regular insulin use. 相似文献970.
Reef fish sustain populations on isolated reefs and show genetic diversity between nearby reefs even though larvae of many species are swept away from the natal site during pelagic dispersal. Retention or recruitment to natal reefs requires orientation capabilities that enable larvae to find their way. Although olfactory and acoustically based orientation has been implicated in homing when larvae are in the reef’s vicinity, it is still unclear how they cope with greater distances. Here we show evidence for a sun compass mechanism that can bring the larvae to the vicinity of their natal reef. In a circular arena, pre-settlement larvae and early settlers (<24 hours) of the cardinal fish, Ostorhinchus doederleini, showed a strong SSE directional swimming response, which most likely has evolved to compensate for the locally prevailing large scale NNW current drift. When fish were clock-shifted 6 hours, they changed their orientation by ca. 180° as predicted by the tropical sun curve at One Tree Island, i.e. they used a time-compensated sun compass. Furthermore, the fish oriented most consistently at times of the day when the sun azimuth is easy to determine. Microsatellite markers showed that the larvae that had just arrived at One Tree Island genetically belonged to either the local reef population or to Fitzroy Reef located 12 kilometers to the SSE. The use of a sun compass adds a missing long-distance link to the hierarchy of other sensory abilities that can direct larvae to the region of origin, including their natal reef. Predominant local recruitment, in turn, can contribute to genetic isolation and potential speciation. 相似文献