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排序方式: 共有591条查询结果,搜索用时 281 毫秒
81.
Kamil J. Kuder Dorota Łażewska Maria Kaleta Gniewomir Latacz Tim Kottke Agnieszka Olejarz Tadeusz Karcz Andrzej Fruziński Katarzyna Szczepańska Janina Karolak-Wojciechowska Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry》2017,25(10):2701-2712
As a continuation of our search for novel histamine H3 receptor ligands a series of twenty new tert-amyl phenoxyalkylamine derivatives (2–21) was synthesized. Compounds of four to eight carbon atoms spacer alkyl chain were evaluated on their binding properties at human histamine H3 receptor (hH3R). The highest affinities were observed for pentyl derivatives 6–8 (Ki = 8.8–23.4 nM range) and among them piperidine derivative 6 with Ki = 8.8 nM. Structures 6, 7 were also classified as antagonists in cAMP accumulation assay (with EC50 = 157 and 164 nM, respectively). Moreover, new compounds were also evaluated for anticonvulsant activity in Antiepileptic Screening Program (ASP) at National Institute of Neurological Disorders and Stroke (USA). Seven compounds (2–4, 9, 11, 12 and 20) showed anticonvulsant activity at maximal electroshock (MES) test in the dose of 30 mg/kg at 0.5 h. In the subcutaneous pentetrazole (scMET) test compound 4 showed protection at 100 and 300 mg/kg dose at mice, however compounds showed high neurotoxicity in rotarod test at used doses. Also, molecular modeling studies were undertaken, to explain affinity of compounds at hH3R (taking into the consideration X-ray analysis of compound 18). In order to estimate “drug-likeness” of selected compounds in silico and experimental evaluation of lipophilicity, metabolic stability and cytotoxicity was performed. 相似文献
82.
Janne Soininen Riku Paavola Janina Kwandrans Timo Muotka 《Biodiversity and Conservation》2009,18(1):79-89
As wholesale biodiversity assessment is often impractical, the use of surrogates that reflect the assemblage structure and
diversity of other taxa has attracted increased attention. We sampled 47 boreal streams for diatoms and macroalgae and examined
their assemblage patterns along major environmental gradients. Our main intention was to examine whether diatoms might be
useful surrogates for macroalgae in boreal streams. We also assessed whether taxon richness and community composition provided
similar insights into the patterns of cross-taxon concordance. According to canonical correspondence analysis, diatom distribution
was most strongly related to water pH, conductivity, latitude and longitude, and macroalgal distribution to water pH and iron
content, latitude and bed instability. In Mantel’s test, diatoms and macroalgae showed significant cross-taxon concordance.
However, there was no significant correlation between taxon richness of the two algal groups, likely reflecting their differing
responses to environmental variables. We found evidence that although diatoms and macroalgae are partly controlled by different
environmental factors, they are segregated rather similarly along latitude and a few environmental gradients such as water
pH and iron content. We conclude that, at least at broad geographical extents and in small streams, diatoms reflect the structure
of the macroalgal community and are therefore useful surrogates for cost-effective biomonitoring of algal communities in streams. 相似文献
83.
Angelica Crottini Janina Dordel Jrn Khler Frank Glaw Andreas Schmitz Miguel Vences 《Molecular phylogenetics and evolution》2009,53(1):345-350
A phylogeny for 29 species of scincine lizards from Madagascar, based on 3693 bp of six mitochondrial and five nuclear genes, revealed multiple parallel evolution of adaptations for a burrowing life, and unexpected relationships of the monotypic genera Androngo and Cryptoscincus. Androngo trivittatus was sister to Pygomeles braconnieri, and Cryptoscincus minimus was deeply nested within the genus Paracontias, all of these being fossorial taxa of elongated bodies and partly or fully reduced limbs. To account for these results, we place Cryptoscincus as a junior synonym of Paracontias, and discuss possible taxonomic consequences that may affect the status of Androngo, once additional data become available. 相似文献
84.
Andreas Weihe Janina Apitz Frank Pohlheim Annabel Salinas-Hartwig Thomas Börner 《Molecular genetics and genomics : MGG》2009,282(6):587-593
Plastidial (pt) and mitochondrial (mt) genes usually show maternal inheritance. Non-Mendelian, biparental inheritance of plastids
was first described by Baur (Z Indukt Abstamm Vererbungslehre 1:330–351, 1909) for crosses between Pelargonium cultivars. We have analyzed the inheritance of pt and mtDNA by examining the progeny from reciprocal crosses of Pelargonium
zonale and P. inquinans using nucleotide sequence polymorphisms of selected pt and mt genes. Sequence analysis of the progeny revealed biparental
inheritance of both pt and mtDNA. Hybrid plants exhibited variegation: our data demonstrate that the inquinans chloroplasts, but not the zonale chloroplasts bleach out, presumably due to incompatibility of the former with the hybrid nuclear genome. Different distribution
of maternal and paternal sequences could be observed in different sectors of the same leaf, in different leaves of the same
plant, and in different plants indicating random segregation and sorting-out of maternal and paternal plastids and mitochondria
in the hybrids. The substantial transmission of both maternal and paternal mitochondria to the progeny turns Pelargonium into a particular interesting subject for studies on the inheritance, segregation and recombination of mt genes. 相似文献
85.
Elisa Cannizzo Aliyah R. Sohani Judith A. Ferry Ephraim P. Hochberg Michael J. Kluk Michelle E. Dorn Craig Sadowski Janessa J. Bucci Adam M. Ackerman Janina A. Longtine Giovanni Carulli Frederic I. Preffer 《Journal of Hematopathology》2009,2(3):163-170
Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient’s follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development. 相似文献
86.
Elzbieta Malarczyk Janina Kochmanska-Rdest Anna Jarosz-Wilkolazka 《Nonlinear biomedical physics》2009,3(1):1-8
Background
Compared to the waveform or spectrum analysis of event-related potentials (ERPs), time-frequency representation (TFR) has the advantage of revealing the ERPs time and frequency domain information simultaneously. As the human brain could be modeled as a complicated nonlinear system, it is interesting from the view of psychological knowledge to study the performance of the nonlinear and linear time-frequency representation methods for ERP research. In this study Hilbert-Huang transformation (HHT) and Morlet wavelet transformation (MWT) were performed on mismatch negativity (MMN) of children. Participants were 102 children aged 8–16 years. MMN was elicited in a passive oddball paradigm with duration deviants. The stimuli consisted of an uninterrupted sound including two alternating 100 ms tones (600 and 800 Hz) with infrequent 50 ms or 30 ms 600 Hz deviant tones. In theory larger deviant should elicit larger MMN. This theoretical expectation is used as a criterion to test two TFR methods in this study. For statistical analysis MMN support to absence ratio (SAR) could be utilized to qualify TFR of MMN. 相似文献87.
Józef Kładny Janina Suchy Ewa Kłujszo-Grabowska Tomasz Kacperski Rodney J. Scott Grzegorz Kurzawski Jan Lubiński 《Cancer epidemiology》2009,33(2):161-163
Background: Genetic predispositions to disease have focused on highly penetrant causative changes in tumor suppressor genes or genes associated with DNA mismatch repair. New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization. Methods: In this report we have examined the tumor characteristics in a group of patients who have been shown to harbor two polymorphisms in two genes that are associated with the immune system NOD2 and TNFα. Results: Colorectal cancers from patients with NOD2 3020insC and TNFα-1031T/T constitutional changes are mostly right-sided disease (OR = 2.21, p = 0.03) with a tendency to higher stages (OR = 2.41, p = 0.06), increased number of associated polyps (OR = 1.77, p = 0.16) and later age of average age of disease onset (p = 0.039). Conclusion: The results reveal that there appear to be specific characteristics associated with the tumors that may aid in determining management strategies to reduce the risk of disease. 相似文献
88.
89.
Susanna Marg Ulrike Winkler Marcello Sestu Mirko Himmel Madeleine Sch?nherr Janina B?r Amrit Mann Markus Moser Claudia T. Mierke Klemens Rottner Manfred Blessing Johannes Hirrlinger Wolfgang H. Ziegler 《PloS one》2010,5(7)
Background
The cytoskeletal adaptor protein vinculin plays a fundamental role in cell contact regulation and affects central aspects of cell motility, which are essential to both embryonal development and tissue homeostasis. Functional regulation of this evolutionarily conserved and ubiquitously expressed protein is dominated by a high-affinity, autoinhibitory head-to-tail interaction that spatially restricts ligand interactions to cell adhesion sites and, furthermore, limits the residency time of vinculin at these sites. To date, no mutants of the vinculin protein have been characterized in animal models.Methodology/Principal Findings
Here, we investigate vinculin-ΔEx20, a splice variant of the protein lacking the 68 amino acids encoded by exon 20 of the vinculin gene VCL. Vinculin-ΔEx20 was found to be expressed alongside with wild type protein in a knock-in mouse model with a deletion of introns 20 and 21 (VCL-ΔIn20/21 allele) and shows defective head-to-tail interaction. Homozygous VCL-ΔIn20/21 embryos die around embryonal day E12.5 showing cranial neural tube defects and exencephaly. In mouse embryonic fibroblasts and upon ectopic expression, vinculin-ΔEx20 reveals characteristics of constitutive head binding activity. Interestingly, the impact of vinculin-ΔEx20 on cell contact induction and stabilization, a hallmark of the vinculin head domain, is only moderate, thus allowing invasion and motility of cells in three-dimensional collagen matrices. Lacking both F-actin interaction sites of the tail, the vinculin-ΔEx20 variant unveils vinculin''s dynamic binding to cell adhesions independent of a cytoskeletal association, and thus differs from head-to-tail binding deficient mutants such as vinculin-T12, in which activated F-actin binding locks the protein variant to cell contact sites.Conclusions/Significance
Vinculin-ΔEx20 is an active variant supporting adhesion site stabilization without an enhanced mechanical coupling. Its presence in a transgenic animal reveals the potential of splice variants in the vinculin gene to alter vinculin function in vivo. Correct control of vinculin is necessary for embryonic development. 相似文献90.
Joshua Schroeder Janina Kueper Kaplan Leon Meir Liebergall 《World journal of stem cells》2015,7(1):186-194
In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer’s disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion. 相似文献