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991.
Penélope González-Sampériz Suzanne A.G. Leroy Santiago Fernández María José Gil-García Blas Valero-Garcés 《Review of Palaeobotany and Palynology》2010,162(3):427-37
A palaeobotanical analysis of the Pleistocene floras and vegetation in the Iberian Peninsula shows the existence of patched landscapes with Pinus woodlands, deciduous and mixed forests, parklands (savannah-like), shrublands, steppes and grasslands. Extinctions of Arctotertiary woody taxa are recorded during the Early and Middle Pleistocene, but glacial refugia facilitated the survival of a number of temperate, Mediterranean and Ibero-North African woody angiosperms. The responses of Iberian vegetation to climatic changes during the Pleistocene have been spatially and temporarily complex, including rapid changes of vegetation in parallel to orbital and suborbital variability, and situations of multi-centennial resilience or accommodation to climatic changes. Regional characteristics emerged as soon as for the Middle Pleistocene, if not earlier: Ericaceae in the Atlantic coast indicating wetter climate, thermo-mediterranean elements in the south as currently, and broad-leaf trees in the northeastern. Overall, steppe landscapes and open Pinus woodlands prevailed over many continental regions during the cold spells of the Late Pleistocene. The maintenance of a high phytodiversity during the glacials was linked to several refuge zones in the coastal shelves of the Mediterranean and intramountainous valleys. Northern Iberia, especially on coastal areas, was also patched with populations of tree species, and this is not only documented by palaeobotanical data (pollen and charcoal) but also postulated by phylogeographical models. 相似文献
992.
Rahim AA Wong AM Buckley SM Chan JK David AL Cooper JD Coutelle C Peebles DM Waddington SN 《Biochemical Society transactions》2010,38(6):1489-1493
The cellular and molecular environment present in the fetus and early newborn provides an excellent opportunity for effective gene transfer. Innate and pre-existing anti-vector immunity may be attenuated or absent and the adaptive immune system predisposed to tolerance towards xenoproteins. Stem cell and progenitor cell populations are abundant, active and accessible. In addition, for treatment of early lethal genetic diseases of the nervous system, the overarching advantage may be that early gene supplementation prevents the onset of irreversible pathological changes. Gene transfer to the fetal mouse nervous system was achieved, albeit inefficiently, as far back as the mid-1980s. Recently, improvements in vector design and production have culminated in near-complete correction of a mouse model of spinal muscular atrophy. In the present article, we review perinatal gene transfer from both a therapeutic and technological perspective. 相似文献
993.
This study examined the contribution of response bias to measures of delay discounting in Long-Evans rats (n = 8) using the adjusting amount procedure. Under this procedure, we assessed preference for 150 μl of 10% sucrose solution delivered following a delay over a variable-amount alternative delivered immediately. Bias was calculated based on relative preference when reinforcers were delivered immediately from both alternatives. We extended this assessment procedure to examine preference when rewards from both alternatives were equally delayed (2, 4, 8, or 16 s) in addition to assessing a traditional delay discounting function. Relative preference was similar across delays and slightly larger than 150 μl. These results indicate that response bias was stable and suggests a relative aversion for the adjusting alternative, which may be due to the variability in reward size associated with that alternative. 相似文献
994.
Prakash SK LeMaire SA Guo DC Russell L Regalado ES Golabbakhsh H Johnson RJ Safi HJ Estrera AL Coselli JS Bray MS Leal SM Milewicz DM Belmont JW 《American journal of human genetics》2010,87(6):743-756
Thoracic aortic aneurysms and dissections (TAAD) cause significant morbidity and mortality, but the genetic origins of TAAD remain largely unknown. In a genome-wide analysis of 418 sporadic TAAD cases, we identified 47 copy number variant (CNV) regions that were enriched in or unique to TAAD patients compared to population controls. Gene ontology, expression profiling, and network analysis showed that genes within TAAD CNVs regulate smooth muscle cell adhesion or contractility and interact with the smooth muscle-specific isoforms of α-actin and β-myosin, which are known to cause familial TAAD when altered. Enrichment of these gene functions in rare CNVs was replicated in independent cohorts with sporadic TAAD (STAAD, n = 387) and inherited TAAD (FTAAD, n = 88). The overall prevalence of rare CNVs (23%) was significantly increased in FTAAD compared with STAAD patients (Fisher's exact test, p = 0.03). Our findings suggest that rare CNVs disrupting smooth muscle adhesion or contraction contribute to both sporadic and familial disease. 相似文献
995.
Prashant Agrawal Suzanne Kiihne Mathias Hofmann Huub de Groot 《生物化学与生物物理学报:生物膜》2010,1798(2):202-4069
Membrane fusion requires restructuring of lipid bilayers mediated by fusogenic membrane proteins. Peptides that correspond to natural transmembrane sequences or that have been designed to mimic them, such as low-complexity “Leu-Val” (LV) peptide sequences, can drive membrane fusion, presumably by disturbing the lipid bilayer structure. Here, we assess how peptides of different fusogenicity affect membrane structure using solid state NMR techniques. We find that the more fusogenic variants induce an unaligned lipid phase component and a large degree of phase separation as observed in 31P 2D spectra. The data support the idea that fusogenic peptides accumulate PE in a non-bilayer phase which may be critical for the induction of fusion. 相似文献
996.
Suzanne C. Mills Alessandro Grapputo Ilmari Jokinen Esa Koskela Tapio Mappes Tanja Poikonen 《Evolution; international journal of organic evolution》2010,64(1):166-179
Trade-offs are widespread between life-history traits, such as reproduction and survival. However, their underlying physiological and behavioral mechanisms are less clear. One proposed physiological factor involves the trade-off between investment in male reproductive effort and immunity. Based on this hypothesis, we investigated differences in fitness between artificially selected immune response bank vole groups, Myodes glareolus . Significant heritability of immune response was found and a correlated response in testosterone levels to selection on immune function. Male reproductive effort, reproductive success, and survival of first generation offspring were assessed and we demonstrate a relationship between laboratory measured immune parameters and fitness parameters in field enclosures. We identify a trade-off between reproductive effort and survival with immune response and parasites as mediators. However, this trade-off results in equal male fitness in natural conditions, potentially demonstrating different male signaling strategies for either reproductive effort or survival. Females gain indirect genetic benefits for either genetic disease resistance or male reproductive effort, but not both. Immune response is genetically variable, genetically linked to testosterone and may indirectly maintain genetic variation for sexually selected traits. Evidence for both a genetic and a field trade-off between reproductive effort and survival indicates an evolutionary constraint on fitness traits. 相似文献
997.
Cameron J. Smith Amjad Ali Liya Chen Milton L. Hammond Matt S. Anderson Ying Chen Suzanne S. Eveland Qiu Guo Sheryl A. Hyland Denise P. Milot Carl P. Sparrow Samuel D. Wright Peter J. Sinclair 《Bioorganic & medicinal chemistry letters》2010,20(1):346-349
A series of 2-arylbenzoxazole inhibitors of the cholesterol ester transfer protein (CETP) is described. Structure–activity studies focused on variation of the substitution of the benzoxazole moiety. Substitution at the 5- and 7-positions of the benzoxazole moiety was found to be beneficial for CETP inhibition. Compound 47 was found to be the most potent inhibitor in this series and inhibited CETP with an IC50 of 28 nM. 相似文献
998.
Lu Z Napolitano JB Theberge A Ali A Hammond ML Tan E Tong X Xu SS Latham MJ Peterson LB Anderson MS Eveland SS Guo Q Hyland SA Milot DP Chen Y Sparrow CP Wright SD Sinclair PJ 《Bioorganic & medicinal chemistry letters》2010,20(24):7469-7472
A new class of CETP inhibitors was designed and prepared. These compounds are potent both in vitro and in vivo. The most active compound (12d) has shown an ability to raise HDL significantly in transgenic mouse PD model. 相似文献
999.
Suzanne Currie Sacha LeBlanc M. Alexandrea Watters Kathleen M. Gilmour 《Proceedings. Biological sciences / The Royal Society》2010,277(1683):905-913
Juvenile salmonid fish readily form dominance hierarchies when faced with limited resources. While these social interactions may result in profound behavioural and physiological stress, it is unknown if this social stress is evident at the level of the cellular stress response—specifically, the induction of stress or heat shock proteins (Hsps). Thus, the goal of our study was to determine if Hsps are induced during hierarchy formation in juvenile rainbow trout (Oncorhynchus mykiss). To this end, we measured levels of three Hsps, Hsp70, Hsc (heat shock cognate)70 and Hsp90 in the white muscle, liver and brain of trout that had been interacting for 36 h, 72 h or 6 days. Our data indicate that Hsps are induced in both dominant and subordinate fish in a time- and tissue-specific manner. In further mechanistic experiments on fasted and cortisol-treated fish, we demonstrated that high plasma cortisol does not affect Hsp induction in trout white muscle or liver, but both conditions may be part of the mechanism for Hsp induction with social stress in the brain. We conclude that the behavioural and physiological stress experienced by juvenile rainbow trout in dominance hierarchies can be extended to the induction of Hsps. 相似文献
1000.
Protein-based vaccines have significant potential as infectious disease and anticancer therapeutics, but clinical impact has been limited in some applications by their inability to generate a coordinated cellular immune response. Here, a pH-responsive carrier incorporating poly(propylacrylic acid) (PPAA) was evaluated to test whether improved cytosolic delivery of a protein antigen could enhance CD8+ cytotoxic lymphocyte generation and prophylactic tumor vaccine responses. PPAA was directly conjugated to the model ovalbumin antigen via reducible disulfide linkages and was also tested in a particulate formulation after condensation with cationic poly(dimethylaminoethyl methacrylate) (PDMAEMA). Intracellular trafficking studies revealed that both PPAA-containing formulations were stably internalized and evaded exocytotic pathways, leading to increased intracellular accumulation and potential access to the cytosolic MHC-1 antigen presentation pathway. In an EG.7-OVA mouse tumor protection model, both PPAA-containing carriers robustly inhibited tumor growth and led to an approximately 3.5-fold increase in the longevity of tumor-free survival relative to controls. Mechanistically, this response was attributed to the 8-fold increase in production of ovalbumin-specific CD8+ T-lymphocytes and an 11-fold increase in production of antiovalbumin IgG. Significantly, this is one of the first demonstrated examples of in vivo immunotherapeutic efficacy using soluble protein-polymer conjugates. These results suggest that carriers enhancing cytosolic delivery of protein antigens could lead to more robust CD8+ T-cell response and demonstrate the potential of pH-responsive PPAA-based carriers for therapeutic vaccine applications. 相似文献