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101.
Pulmonary expression of voltage-gated calcium channels: special reference to sensory airway receptors 总被引:3,自引:2,他引:1
De Proost I Brouns I Pintelon I Timmermans JP Adriaensen D 《Histochemistry and cell biology》2007,128(4):301-316
Studying depolarisation induced calcium entry in our recently developed in situ lung slice model for molecular live cell imaging of selectively visualised pulmonary neuroepithelial bodies (NEBs), exemplified the need for information on the localisation of voltage-gated calcium channels (Ca(v)) in lungs in general, and related to sensory airway receptors more specifically. The present study therefore aimed at identifying the expression pattern of all major classes and subtypes of Ca(v) channels, using multiple immunostaining of rat lung cryosections. Ca(v) channel antibodies were combined with antibodies that selectively label NEBs, nerve fibre populations, smooth muscle, endothelium and Clara cells. Ca(v)2.1 (P/Q-type) was the only Ca(v) channel expressed in NEB cell membranes, and appeared to be restricted to the apical membrane of the slender NEB cell processes that reach the airway lumen. Subpopulations of the vagal but not the spinal sensory nerve fibres that contact NEBs showed immunoreactivity (IR) for Ca(v)1.2 (L-type) and Ca(v)2.1. Ca(v)2.3 (R-type) was selectively expressed by the so-called Clara-like cells that cover NEBs only, and appears to be a unique marker to discriminate this epithelial cell type from the much more extensive group of Clara cells in rat airways. The laminar nerve endings of smooth muscle-associated airway receptors (SMARs) revealed IR for both Ca(v)2.1 and Ca(v)2.2 (N-type). More generally, Ca(v)1.2 was seen to be expressed in vascular smooth muscle, Ca(v)2.3 and Ca(v)3.1 (T-type) in bronchial smooth muscle, Ca(v)3.1 and Ca(v)3.2 (T-type) in endothelial cells, and Ca(v)1.3 (L-type) in a limited number of epithelial cells. In conclusion, the present immunocytochemical study has demonstrated that the various subtypes of Ca(v) channels have distinct expression patterns in rat lungs. Special focus on morphologically/neurochemically characterised sensory airway receptors learned us that both NEBs and SMARs present Ca(v) channels. Knowledge of the identification and localisation of Ca(v) channels in airway receptors and surrounding tissues provides a solid basis for interpretation of the calcium mediated activation studied in our ex vivo lung slice model. 相似文献
102.
Chaperoning Anfinsen: the steric foldases 总被引:1,自引:0,他引:1
Some proteins are so much resistant to proteolysis and unfolding that they violate folding rules shared by the vast majority of proteins. These unusual proteins manage to fold into an active native conformation that is thermodynamically at best marginally, but often even less stable than the unfolded state. A huge energetic barrier traps these proteins kinetically in the folded state. The drawback of this situation is the need for a specialized chaperone that adds steric information to the proteins to cross this barrier on the folding pathway. Until now, our knowledge of these intriguing chaperones was restricted to the prodomains of secreted proteases, which function intramolecularly. Recent research has added more examples, which now include the membrane-anchored lipase-specific foldase and the pilus subunit specific chaperone, both acting intermolecularly. The case of the pilin chaperone is somewhat deviant in that steric information is definitely provided, but the pilus subunit adopts a thermodynamically favourable stable conformation. 相似文献
103.
Silomon M Bauer I Bauer M Nolting J Paxian M Rensing H 《Cellular & molecular biology letters》2007,12(1):25-38
Stress response genes including heat shock proteins are induced under a variety of conditions to confer cellular protection.
This study investigated the role of calcium signaling in the induction of two stress response genes, heme oxygenase-1/hsp32
and hsp70, in isolated rat hepatocytes. Both genes were induced by cellular glutathione depletion. This induction could be
inhibited by BAPTA-AM. Culturing in a calcium-free medium prevented the induction of hsp70 gene expression after glutathione
depletion without affecting heme oxygenase-1 gene expression. Thapsigargin increased the gene expression of heme oxygenase-1
but not that of hsp70. Thapsigargin-induced heme oxygenase-1 induction was completely inhibited by BAPTA-AM. Incubation with
the Ca2+-ionophore A23187 augmented heme oxygenase-1 (two-fold) and hsp70 (5.2-fold) mRNA levels. Our data suggests a significant
role of Ca2+-dependent pathways in the induction of the two stress genes. An increase in the cytoplasmic Ca2+ activity seems to play a key role in the cascade of signaling leading to the induction of the two genes. However, the source
of Ca2+ that fluxes into the cytoplasm seems to be different. Our data provides evidence for a compartmentalization of calcium fluxes,
i.e. the Ca2+ flux from intracellular stores (e.g. the endoplasmic reticulum) plays a major role in the induction of heme oxygenase-1.
By contrast, Ca2+ flux from the extracellular medium seems to be a mechanism initiating the cellular signaling cascade leading to hsp70 gene
induction. 相似文献
104.
Sheila L. MacRae Quanwei Zhang Christophe Lemetre Inge Seim Robert B. Calder Jan Hoeijmakers Yousin Suh Vadim N. Gladyshev Andrei Seluanov Vera Gorbunova Jan Vijg Zhengdong D. Zhang 《Aging cell》2015,14(2):288-291
Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM‐associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long‐lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR. 相似文献
105.
Inge Everaert Antien Mooyaart Audrey Baguet Ana Zutinic Hans Baelde Eric Achten Youri Taes Emile De Heer Wim Derave 《Amino acids》2011,40(4):1221-1229
Carnosine is found in high concentrations in skeletal muscles, where it is involved in several physiological functions. The
muscle carnosine content measured within a population can vary by a factor 4. The aim of this study was to further characterize
suggested determinants of the muscle carnosine content (diet, gender and age) and to identify new determinants (plasma carnosinase
activity and testosterone). We investigated a group of 149 healthy subjects, which consisted of 94 men (12 vegetarians) and
55 women. Muscle carnosine was quantified in M. soleus, gastrocnemius and tibialis anterior using magnetic resonance proton
spectroscopy and blood samples were collected to determine CNDP1 genotype, plasma carnosinase activity and testosterone concentrations. Compared to women, men have 36, 28 and 82% higher
carnosine concentrations in M. soleus, gastrocnemius and tibialis anterior muscle, respectively, whereas circulating testosterone
concentrations were unrelated to muscle carnosine levels in healthy men. The carnosine content of the M. soleus is negatively
related to the subjects’ age. Vegetarians have a lower carnosine content of 26% in gastrocnemius compared to omnivores. In
contrast, there is no difference in muscle carnosine content between omnivores with a high or low ingestion of β-alanine.
Muscle carnosine levels are not related to the polymorphism of the CNDP1 gene or to the enzymatic activity of the plasma carnosinase. In conclusion, neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content, whereas vegetarianism,
female gender and increasing age are the factors associated with reduced muscle carnosine stores. 相似文献
106.
Junker N Andersen MH Wenandy L Dombernowsky SL Kiss K Sørensen CH Therkildsen MH Von Buchwald C Andersen E Straten PT Svane IM 《Cytotherapy》2011,13(7):822-834
Background aimsAdoptive transfer of tumor-infiltrating lymphocytes (TIL) has proven effective in metastatic melanoma and should therefore be explored in other types of cancer. The aim of this study was to examine the feasibility of potentially expanding clinically relevant quantities of tumor-specific T-cell cultures from TIL from patients with head and neck squamous cell carcinoma (HNSCC) using a more rapid expansion procedure compared with previous HNSCC studies.MethodsIn a two-step expansion process, initially TIL bulk cultures were established from primary and recurrent HNSCC tumors in high-dose interleukin (IL)-2. Secondly, selected bulk cultures were rapidly expanded using anti-CD3 antibody, feeder cells and high-dose IL-2. T-cell subsets were phenotypically characterized using flow cytometry. T-cell receptor (TCR) clonotype mapping was applied to examine clonotype dynamics during culture. Interferon (INF)-γ detection by Elispot and Cr51 release assay determined the specificity and functional capacity of selected TIL pre- and post-rapid expansion.ResultsTIL bulk cultures were expanded in 80% of the patients included, showing tumor specificity in 60% of the patients. Rapid expansions generated up to 3500-fold expansion of selected TIL cultures within 17 days. The cultures mainly consisted of T-effector memory cells, with varying distributions of CD8+ and CD4+ subtypes both among cultures and patients. TCR clonotype mapping demonstrated oligoclonal expanded cultures, ranging from approximately 10 to 30 T-cell clonotypes. TIL from large-scale rapid expansions maintained functional capacity, and contained tumor-specific T cells.ConclusionThe procedure is feasible for expansion of TIL from HNSCC, ensuring clinically relevant expansion folds within 7 weeks. The cell culture kinetics and phenotypes of the TIL resemble previously published results on TIL from melanoma, setting the stage for clinical testing of this promising treatment strategy for patients with HNSCC. 相似文献
107.
108.
Satoh M Bjerkås I Haugarvoll E Chan EK Szabo NJ Jirillo E Poppe TT Sveier H Tørud B Koppang EO 《Fish & shellfish immunology》2011,30(4-5):1080-1086
The introduction of oil-adjuvanted vaccines in salmon aquaculture made large-scale production feasible by reducing the impact of infections. Vaccines given intraperitoneally (ip) contain oil adjuvant such as mineral oil. However, in rodents, a single ip injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome. We have recently reported that autoimmune disease in farmed salmon, characterized by production of various autoantibodies, immune complex glomerulonephritis, liver thrombosis, and spinal deformity, are previously unrecognized side effects of vaccination. In the present study, we examined whether vaccination-induced autoantibody production in farmed Atlantic salmon is a mere result of polyclonal B-cell activation. Sera were collected from 205 vaccinated and unvaccinated Atlantic salmon (experimental, 7 farms) and wild salmon. Total IgM levels and autoantibodies to salmon blood cell (SBC) extract in sera were measured by ELISA and the relationship between hypergammaglobulinemia and autoantibody production was analyzed. Comparison of endpoint titers vs levels/units using a single dilution of sera in detection of autoantibodies to SBC showed near perfect correlation, justifying the use of the latter for screening. Both total IgM and anti-SBC antibodies are increased in vaccinated salmon compared with unvaccinated controls, however, they do not always correlate well when compared between groups or between individuals, suggesting the involvement of antigen-specific mechanisms in the production of anti-SBC autoantibodies. The primary considerations of successful vaccine for aquaculture are cost-effectiveness and safety. Vaccination-induced autoimmunity in farmed Atlantic salmon may have consequences on future vaccine development and salmon farming strategy. Evaluation for polyclonal hypergamamglobulinemia and autoimmunity should be included as an important trait when vaccine efficacy and safety are evaluated in future. 相似文献
109.
110.