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121.
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Effects of a 2‐year behavioral weight loss intervention on sleep and mood in obese individuals treated in primary care practice
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123.
Colton Hall Hannah Wolfe Alyssa Wells Huan-Chieh Chien Claire Colas Avner Schlessinger Kathleen M. Giacomini Allen A. Thomas 《Bioorganic & medicinal chemistry letters》2019,29(16):2254-2258
A series of 1,2,3-triazole analogs of the amino acids l-histidine and l-tryptophan were modeled, synthesized and tested for l-type amino acid transporter 1 (LAT1; SLC7A5) activity to guide the design of amino acid-drug conjugates (prodrugs). These triazoles were conveniently prepared by the highly convergent Huisgen 1,3-dipolar cycloaddition (Click Chemistry). Despite comparable predicted binding modes, triazoles generally demonstrated reduced cell uptake and LAT1 binding potency relative to their natural amino acid counterparts. The structure-activity relationship (SAR) data for these triazoles has important ramifications for treating cancer and brain disorders using amino acid prodrugs or LAT1 inhibitors. 相似文献
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Alyssa R. Borges Daniel A. Toledo Bruno R. Fermino Jos Carlos de Oliveira Ariel Mariano Silber Maria Carolina Elias Heloisa D'Avila Kzia K. G. Scopel 《The Journal of eukaryotic microbiology》2019,66(3):385-392
Since the observation of the great pleomorphism of fish trypanosomes, in vitro culture has become an important tool to support taxonomic studies investigating the biology of cultured parasites, such as their structure, growth dynamics, and cellular cycle. Relative to their biology, ex vivo and in vitro studies have shown that these parasites, during the multiplication process, duplicate and segregate the kinetoplast before nucleus replication and division. However, the inverse sequence (the nucleus divides before the kinetoplast) has only been documented for a species of marine fish trypanosomes on a single occasion. Now, this previously rare event was observed in Trypanosoma abeli, a freshwater fish trypanosome. Specifically, from 376 cultured parasites in the multiplication process, we determined the sequence of organelle division for 111 forms; 39% exhibited nucleus duplication prior to kinetoplast replication. Thus, our results suggest that nucleus division before the kinetoplast may not represent an accidental or erroneous event occurring in the main pathway of parasite reproduction, but instead could be a species‐specific process of cell biology in trypanosomes, such as previously noticed for Leishmania. This “alternative” pathway for organelle replication is a new field to be explored concerning the biology of marine and freshwater fish trypanosomes. 相似文献
126.
Alice Rogers Alastair R. Harborne Christopher J. Brown Yves‐Marie Bozec Carolina Castro Iliana Chollett Karlo Hock Cheryl A. Knowland Alyssa Marshell Juan C. Ortiz Tries Razak George Roff Jimena Samper‐Villarreal Megan I. Saunders Nicholas H. Wolff Peter J. Mumby 《Global Change Biology》2015,21(2):504-514
Under projections of global climate change and other stressors, significant changes in the ecology, structure and function of coral reefs are predicted. Current management strategies tend to look to the past to set goals, focusing on halting declines and restoring baseline conditions. Here, we explore a complementary approach to decision making that is based on the anticipation of future changes in ecosystem state, function and services. Reviewing the existing literature and utilizing a scenario planning approach, we explore how the structure of coral reef communities might change in the future in response to global climate change and overfishing. We incorporate uncertainties in our predictions by considering heterogeneity in reef types in relation to structural complexity and primary productivity. We examine 14 ecosystem services provided by reefs, and rate their sensitivity to a range of future scenarios and management options. Our predictions suggest that the efficacy of management is highly dependent on biophysical characteristics and reef state. Reserves are currently widely used and are predicted to remain effective for reefs with high structural complexity. However, when complexity is lost, maximizing service provision requires a broader portfolio of management approaches, including the provision of artificial complexity, coral restoration, fish aggregation devices and herbivore management. Increased use of such management tools will require capacity building and technique refinement and we therefore conclude that diversification of our management toolbox should be considered urgently to prepare for the challenges of managing reefs into the 21st century. 相似文献
127.
Tripathy R Reiboldt A Messina PA Iqbal M Singh J Bacon ER Angeles TS Yang SX Albom MS Robinson C Chang H Ruggeri BA Mallamo JP 《Bioorganic & medicinal chemistry letters》2006,16(8):2158-2162
Structural analysis of the essential binding elements of the oxindole-based kinase inhibitor (1) led to the identification of a novel class of heterocyclic-substituted pyrazolones. Knoevenagel condensation of a variety of activated methylene nucleophiles with indole or pyrrole carboxaldehydes provided a focused library of molecules, each containing elements of kinase pharmacophore probe. Initial screening for VEGFR-2 kinase inhibition eliminated several of the probes. Identification of an active pyrazolone motif and further optimization resulted in several highly potent VEGFR-2 inhibitors with cellular efficacy, anti-angiogenic activity ex vivo in rat aortic ring explant cultures, and oral anti-tumor efficacy in nude mice. 相似文献
128.
The extensive diversity of Plasmodium falciparum antigens is a major obstacle to a broadly effective malaria vaccine but population genetics has rarely been used to guide vaccine design. We have completed a meta-population genetic analysis of the genes encoding ten leading P. falciparum vaccine antigens, including the pre-erythrocytic antigens csp, trap, lsa1 and glurp; the merozoite antigens eba175, ama1, msp''s 1, 3 and 4, and the gametocyte antigen pfs48/45. A total of 4553 antigen sequences were assembled from published data and we estimated the range and distribution of diversity worldwide using traditional population genetics, Bayesian clustering and network analysis. Although a large number of distinct haplotypes were identified for each antigen, they were organized into a limited number of discrete subgroups. While the non-merozoite antigens showed geographically variable levels of diversity and geographic restriction of specific subgroups, the merozoite antigens had high levels of diversity globally, and a worldwide distribution of each subgroup. This shows that the diversity of the non-merozoite antigens is organized by physical or other location-specific barriers to gene flow and that of merozoite antigens by features intrinsic to all populations, one important possibility being the immune response of the human host. We also show that current malaria vaccine formulations are based upon low prevalence haplotypes from a single subgroup and thus may represent only a small proportion of the global parasite population. This study demonstrates significant contrasts in the population structure of P. falciparum vaccine candidates that are consistent with the merozoite antigens being under stronger balancing selection than non-merozoite antigens and suggesting that unique approaches to vaccine design will be required. The results of this study also provide a realistic framework for the diversity of these antigens to be incorporated into the design of next-generation malaria vaccines. 相似文献
129.
Cultured DRGs in different gel scaffolds were analyzed using CA RS microscopy to determine its possible use as a label-free imaging option for tracking cellular growth in a gel scaffold. This study demonstrates for the first time the applicability of CA RS microscopy to the imaging of live neuronal cells in GAG hydrogels. By tuning the laser beating frequency, ωp-ωs, to match the vibration of C–H bonds in the cell membrane, the CA RS signal yields detailed, high-quality images of neurites with single membrane detection sensitivity. The results demonstrate that CA RS imaging allows monitoring of cellular growth in a tissue scaffold over time, with a contrast that shows comparable cellular structures to those obtained using standard fluorescent staining techniques. These findings show the potential of CARS microscopy to assist in the understanding of organogenesis processes in a tissue scaffold.Key words: dorsal root ganglia, neuronal growth, coherent anti-stokes raman scattering, nonlinear optical microscopy, label-free imaging, chondroitin sulfate, hyaluronic acid, poly(ethylene glycol) hydrogel 相似文献
130.
Celine S. Lages Ian Lewkowich Alyssa Sproles Marsha Wills‐Karp Claire Chougnet 《Aging cell》2010,9(5):785-798
Programmed cell death‐1 (PD‐1) is a newly characterized negative regulator of immune responses. The interaction of PD‐1 with its ligands (PD‐L1 and PD‐L2) inhibits T‐cell proliferation and cytokine production in young mice. Increased PD‐1 expression has been described during chronic infections, inducing chronic activation of the immune system to control it. As aging is associated with chronic immune activation, PD‐1 may contribute to age‐associated T‐cell dysfunction. Our data showed the following results in aged mice: (i) the number of PD‐1‐expressing T cells and the level of expression of PD‐Ls was increased on dendritic cell subsets and T cells; (ii) PD‐1+ T cells were exhausted effector memory T cells, as shown by their lower level of CD127, CD25 and CD28, as well as their limited proliferative and cytokine‐producing capacity; (iii) the expression of PD‐1 was up‐regulated after T‐cell receptor‐mediated activation of CD8+ T cells, but not of CD4+ T cells; (iv) blockade of the PD‐1/PD‐L1 pathway moderately improved the cytokine production of T cells from old mice but did not restore their proliferation; and (v) blockade of the PD‐1/PD‐L1 pathway did not restore function of PD‐1+ T cells; its effect appeared to be exclusively mediated by increased functionality of the PD‐1? T cells. Our data thus suggest that blockade of the PD‐1/PD‐L1 is not likely to be efficient at restoring exhausted T‐cell responses in aged hosts, although improving the responses of PD‐1? T cells may prove to be a helpful strategy in enhancing primary responses. 相似文献