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51.
Richard B. Lanman Stefanie A. Mortimer Oliver A. Zill Dragan Sebisanovic Rene Lopez Sibel Blau Eric A. Collisson Stephen G. Divers Dave S. B. Hoon E. Scott Kopetz Jeeyun Lee Petros G. Nikolinakos Arthur M. Baca Bahram G. Kermani Helmy Eltoukhy AmirAli Talasaz 《PloS one》2015,10(10)
Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital SequencingTM is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient’s cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing. 相似文献
52.
Improved media for normal human muscle satellite cells: Serum-free clonal growth and enhanced growth with low serum 总被引:5,自引:0,他引:5
Richard G. Ham Judy A. St. Clair Cecelia Webster Helen M. Blau 《In vitro cellular & developmental biology. Plant》1988,24(8):833-844
Summary We have developed a serum-free medium for clonal growth of normal human muscle satellite cells (HMSC). It consists of an optimized
nutrient medium MCDB 120, plus a serum-free supplement, designated SF, that contains epidermal growth factor (EGF), insulin,
dexamethasone, bovine serum albumin, and fetuin. Fibroblast growth factor was needed with dialyzed fetal bovine serum (dFBS)
as the only other supplement, but in media containing SF, it was only slightly beneficial, and was omitted from the final
medium without significant loss. Clonal growth of HMSC in MCDB 120 plus SF is as good as with 15% serum and 0.5% chicken embryo
or bovine pituitary extract. However, growth is further improved by use of a doubly-supplemented (DS) medium containing both
SF and 5% dFBS. Clonal growth of HMSC in the DS medium far exceeds that in previous media with any amount of serum, and monolayer
growth is at least equal to that in conventional media with higher levels of serum. Cells grown in these media exhibit little
differentiation, even when grown to high densities. However, they retain the capacity for extensive fusion and synthesis of
increased creatine kinase when transferred to a serum-free differentiation-promoting medium, such as Dulbecco's modified Eagle's
medium plus insulin. All experiments were done with clonal cultures of HMSC to insure that observed growth responses were
always those of muscle cells.
This research was supported by a grant from the Muscular, Dystrophy Association.
Editor's statement This article describes the optimization of both the basal nutrient medium and growth factor requirements
for human muscle cells in vitro. This system is critical for studies of normal muscle cell and molecular biology, as well
as for understanding diseases of muscle such as Duchenne, Muscular Dystrophy. 相似文献
53.
Amir Sherman Ravit Eshed Rotem Harel-Beja Galil Tzuri Vitaly Portnoy Shahar Cohen Mor Rubinstein Arthur A. Schaffer Joseph Burger Nurit Katzir Ron Ophir 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2013,126(2):349-358
The availability of sequence information for many plants has opened the way to advanced genetic analysis in many non-model plants. Nevertheless, exploration of genetic variation on a large scale and its use as a tool for the identification of traits of interest are still rare. In this study, we combined a bulk segregation approach with our own-designed microarrays to map the pH locus that influences fruit pH in melon. Using these technologies, we identified a set of markers that are genetically linked to the pH trait. Further analysis using a set of melon cultivars demonstrated that some of these markers are tightly linked to the pH trait throughout our germplasm collection. These results validate the utility of combining microarray technology with a bulk segregation approach in mapping traits of interest in non-model plants. 相似文献
54.
B N Walters T T Lao V A Smith K Blau M de Swiet 《BMJ (Clinical research ed.)》1983,287(6401):1302-1303
55.
56.
Carmi Y Rinott G Dotan S Elkabets M Rider P Voronov E Apte RN 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(6):3462-3471
Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression/metastasis. In this study, we have assessed the role of IL-1 and IL-17 in the control of antitumor immunity versus progression in a model of experimental lung metastasis, using 3LL and B16 epithelial tumor cells. The absence of IL-1 signaling or its excess in the lung microenvironment (in IL-1β and IL-1R antagonist knockout [KO] mice, respectively) resulted in a poor prognosis and reduced T cell activity, compared with WT mice. In IL-1β KO mice, enhanced T regulatory cell development/function, due to a favorable in situ cytokine network and impairment in APC maturation, resulted in suppressed antitumor immunity, whereas in IL-1R antagonist KO mice, enhanced accumulation and activity of myeloid-derived suppressor cells were found. Reduced tumor progression along with improved T cell function was found in IL-17 KO mice, compared with WT mice. In the microenvironment of lung tumors, IL-1 induces IL-17 through recruitment of γ/δ T cells and their activation for IL-17 production, with no involvement of Th17 cells. These interactions were specific to the microenvironment of lung tumors, as in intrafootpad tumors in IL-1/IL-17 KO mice, different patterns of invasiveness were observed and no IL-17 could be locally detected. The results highlight the critical and unique role of IL-1, and cytokines induced by it such as IL-17, in determining the balance between inflammation and antitumor immunity in specific tumor microenvironments. Also, we suggest that intervention in IL-1/IL-17 production could be therapeutically used to tilt this balance toward enhanced antitumor immunity. 相似文献
57.
GROmaρs: A GROMACS-Based Toolset to Analyze Density Maps Derived from Molecular Dynamics Simulations
Rodolfo Briones Christian Blau Carsten Kutzner Bert L. de Groot Camilo Aponte-Santamaría 《Biophysical journal》2019,116(1):4-11
We introduce a computational toolset, named GROmaρs, to obtain and compare time-averaged density maps from molecular dynamics simulations. GROmaρs efficiently computes density maps by fast multi-Gaussian spreading of atomic densities onto a three-dimensional grid. It complements existing map-based tools by enabling spatial inspection of atomic average localization during the simulations. Most importantly, it allows the comparison between computed and reference maps (e.g., experimental) through calculation of difference maps and local and time-resolved global correlation. These comparison operations proved useful to quantitatively contrast perturbed and control simulation data sets and to examine how much biomolecular systems resemble both synthetic and experimental density maps. This was especially advantageous for multimolecule systems in which standard comparisons like RMSDs are difficult to compute. In addition, GROmaρs incorporates absolute and relative spatial free-energy estimates to provide an energetic picture of atomistic localization. This is an open-source GROMACS-based toolset, thus allowing for static or dynamic selection of atoms or even coarse-grained beads for the density calculation. Furthermore, masking of regions was implemented to speed up calculations and to facilitate the comparison with experimental maps. Beyond map comparison, GROmaρs provides a straightforward method to detect solvent cavities and average charge distribution in biomolecular systems. We employed all these functionalities to inspect the localization of lipid and water molecules in aquaporin systems, the binding of cholesterol to the G protein coupled chemokine receptor type 4, and the identification of permeation pathways through the dermicidin antimicrobial channel. Based on these examples, we anticipate a high applicability of GROmaρs for the analysis of molecular dynamics simulations and their comparison with experimentally determined densities. 相似文献
58.
Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury 总被引:54,自引:0,他引:54
Adult bone marrow-derived cells (BMDC) are shown to contribute to muscle tissue in a step-wise biological progression. Following irradiation-induced damage, transplanted GFP-labeled BMDC become satellite cells: membrane-ensheathed mononucleate muscle stem cells. Following a subsequent exercise-induced damage, GFP-labeled multinucleate myofibers are detected. Isolated GFP-labeled satellite cells are heritably myogenic. They express three characteristic muscle markers, are karyotypically diploid, and form clones that can fuse into multinucleate cells in culture or into myofibers after injection into mouse muscles. These results suggest that two temporally distinct injury-related signals first induce BMDC to occupy the muscle stem cell niche and then to help regenerate mature muscle fibers. The stress-induced progression of BMDC to muscle satellite cell to muscle fiber results in a contribution to as many as 3.5% of muscle fibers and is due to developmental plasticity in response to environmental cues. 相似文献
59.
Hagit Hak Hagai Raanan Shahar Schwarz Yifat Sherman Savithramma P. Dinesh-Kumar Ziv Spiegelman 《Molecular Plant Pathology》2023,24(8):838-848
The tomato Tm-22 gene was considered to be one of the most durable resistance genes in agriculture, protecting against viruses of the Tobamovirus genus, such as tomato mosaic virus (ToMV) and tobacco mosaic virus (TMV). However, an emerging tobamovirus, tomato brown rugose fruit virus (ToBRFV), has overcome Tm-22, damaging tomato production worldwide. Tm-22 encodes a nucleotide-binding leucine-rich repeat (NLR) class immune receptor that recognizes its effector, the tobamovirus movement protein (MP). Previously, we found that ToBRFV MP (MPToBRFV) enabled the virus to overcome Tm-22-mediated resistance. Yet, it was unknown how Tm-22 remained durable against other tobamoviruses, such as TMV and ToMV, for over 60 years. Here, we show that a conserved cysteine (C68) in the MP of TMV (MPTMV) plays a dual role in Tm-22 activation and viral movement. Substitution of MPToBRFV amino acid H67 with the corresponding amino acid in MPTMV (C68) activated Tm-22-mediated resistance. However, replacement of C68 in TMV and ToMV disabled the infectivity of both viruses. Phylogenetic and structural prediction analysis revealed that C68 is conserved among all Solanaceae-infecting tobamoviruses except ToBRFV and localizes to a predicted jelly-roll fold common to various MPs. Cell-to-cell and subcellular movement analysis showed that C68 is required for the movement of TMV by regulating the MP interaction with the endoplasmic reticulum and targeting it to plasmodesmata. The dual role of C68 in viral movement and Tm-22 immune activation could explain how TMV was unable to overcome this resistance for such a long period. 相似文献
60.
Synthesis and evaluation of phenoxy acetic acid derivatives as [corrected] anti-mycobacterial agents
Shaharyar M yar MS Siddiqui AA Ali MA 《Bioorganic & medicinal chemistry letters》2006,16(17):4571-4574
In present investigation, 2-(4-formyl-2-methoxyphenoxy) acetic acid on condensation with various ketones in methanolic KOH solution yielded the corresponding chalcones (1-3). These corresponding chalcones were reacted with appropriate acid hydrazide in glacial acetic acid led to the formation of phenoxy acetic acid derivatives. All newly synthesized compounds were evaluated for their anti-mycobacterial activities against Mycobacterium tuberculosis H(37)Rv. 相似文献