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61.
Magdalena N. Muchlinski Emily L. Durham Timothy D. Smith Anne M. Burrows 《American journal of physical anthropology》2013,150(2):301-312
Macrovibrissae are specialized tactile sensory hairs present in most mammalian orders, used in maxillary mechanoreception or “face touch.” Some mammals have highly organized vibrissae and are able to “whisk” them. Movement of vibrissae is influenced by intrinsic vibrissa musculature, striated muscle bands that attach directly to the vibrissa capsule. It is unclear if primates have organized vibrissae or intrinsic vibrissa musculature and it is uncertain if they can move their vibrissae. The present study used histomorphological techniques to compare vibrissae among 19 primates and seven non‐primate mammalian taxa. Upper lips of these mammals were sectioned and processed for histochemical analysis. While controlling for phylogenetic effects the following hypotheses were tested: 1) mammals with well‐organized vibrissae possess intrinsic vibrissa musculature and 2) intrinsic vibrissa musculature is best developed in nocturnal, arboreal taxa. Our qualitative analyses show that only arboreal, nocturnal prosimians possess intrinsic musculature. Not all taxa that possessed organized vibrissae had intrinsic vibrissa musculature. Phylogenetic comparative analyses revealed a 70% probability that stem mammals, primates, and haplorhines possessed intrinsic vibrissa musculature and well‐organized vibrissae. These two traits most likely coevolved according to a discrete phylogenetic analysis. These results indicate that nocturnal, arboreal primates have the potential to more actively use their vibrissae in spatial recognition and navigation tasks than diurnal, more terrestrial species, but there is a clear phylogenetic signal involved in the evolution of primate vibrissae and “face touch.” Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
62.
Elin Grundberg Eshwar Meduri Johanna?K. Sandling ?sa?K. Hedman Sarah Keildson Alfonso Buil Stephan Busche Wei Yuan James Nisbet Magdalena Sekowska Alicja Wilk Amy Barrett Kerrin?S. Small Bing Ge Maxime Caron So-Youn Shin the Multiple Tissue Human Expression Resource Consortium Mark Lathrop Emmanouil T. Dermitzakis Mark I. McCarthy Timothy D. Spector Jordana T. Bell Panos Deloukas 《American journal of human genetics》2013,93(5):876-890
Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Human Expression Resource (MuTHER) and generated Illumina 450K adipose methylome data from 648 twins. We found that individual CpGs had low variance and that variability was suppressed in promoters. We noted that DNA methylation variation was highly heritable (h2median = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. These associations were bidirectional, but there were pronounced negative associations for promoter CpGs. Integration of metQTL with adipose reference epigenomes and disease associations revealed significant enrichment of metQTL overlapping metabolic-trait or disease loci in enhancers (the strongest effects were for high-density lipoprotein cholesterol and body mass index [BMI]). We followed up with the BMI SNP rs713586, a cg01884057 metQTL that overlaps an enhancer upstream of ADCY3, and used bisulphite sequencing to refine this region. Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner. 相似文献
63.
Barbara Pietrzak Anna Bednarska Magdalena Markowska Maciej Rojek Ewa Szymanska Miroslaw Slusarczyk 《Hydrobiologia》2013,715(1):125-134
The combined effect of external environment and energy allocation strategy of the organism on longevity can be exceptional. In a cold oligotrophic fishless habitat, individual Daphnia can live for over a year, several times the usual Daphnia lifespan. This extreme lifespan is in part a consequence of the overwintering strategy which includes storing resources and delaying reproduction until another spring. Yet, contrasting strategies may be applied by Daphnia, resulting in over twofold differences in lifespan within a single habitat. We identify physiological mechanisms mediating such differences in longevity in closely related Daphnia of two lineages coexisting within a high altitude lake, testing the predictions that long-lived animals stay in colder waters and have lower metabolic rates, irrespective of temperature. Vertical distribution of the animals was assessed during three summer stratification seasons, and metabolic activity was measured as oxygen consumption and RNA:DNA ratio. The results not only support our predictions but also reveal that habitat choice is dependent on reproductive status rather than genotype. The young individuals of the overwintering lineage may delay reproduction in part by staying in colder waters than the reproducing adults, which together with low intrinsic metabolic rates may underlie the longevity of Daphnia of this lineage. 相似文献
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65.
Helen Thomas Konrad Beck Magdalena Adamczyk Pascale Aeschlimann Martin Langley Radu C. Oita Lars Thiebach Martin Hils Daniel Aeschlimann 《Amino acids》2013,44(1):161-177
Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca2+ and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca2+ and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons. 相似文献
66.
Jorge Soriano Angeles Villanueva Juan C. Stockert Magdalena Cañete 《Histochemistry and cell biology》2013,139(1):149-160
It is generally accepted that compounds of nanomolecular size penetrate into cells by different endocytic processes. The vehiculization strategy of a compound is a factor that could determine its uptake mechanism. Understanding the influence of the vehicle in the precise mechanism of drug penetration into cells makes possible to improve or modify the therapeutic effects. In this study, using human A-549 cells, we have characterized the possible internalization mechanism of the photosensitizer Zn(II)-phthalocyanine (ZnPc), either dissolved in dimethylformamide (ZnPc–DMF) or included in liposomes of dipalmitoyl-phosphatidyl-choline. Specific inhibitors involved in the main endocytic pathways were used. Co-incubation of cells with ZnPc–liposomes and dynasore (dinamin-mediated endocytosis inhibitor) resulted in a significant decrease of photodamage, whereas other inhibitors did not alter the photodynamic effect of ZnPc. On the contrary, cells treated with ZnPc–DMF in the presence of dynasore, genistein (caveolin-mediated endocytosis inhibitor) or cytochalasin D (macropinocytosis and caveolin-mediated endocytosis inhibitor) showed a significant decrease in ZnPc uptake and photodynamic damage. These results suggest that ZnPc–DMF penetrates into cells mainly by caveolin-mediated endocytosis, whereas ZnPc–liposomes are internalized into cells preferentially by clathrin-mediated endocytosis. We conclude that using different drug vehiculization systems, it is possible to modify the internalization mechanism of a therapeutic compound, which could be of great interest in clinical research. 相似文献
67.
Magdalena Banas Katarzyna Zabieglo Gopinath Kasetty Monika Kapinska-Mrowiecka Julia Borowczyk Justyna Drukala Krzysztof Murzyn Brian A. Zabel Eugene C. Butcher Jens M. Schroeder Artur Schmidtchen Joanna Cichy 《PloS one》2013,8(3)
Chemerin, a chemoattractant ligand for chemokine-like receptor 1 (CMKLR1) is predicted to share similar tertiary structure with antibacterial cathelicidins. Recombinant chemerin has antimicrobial activity. Here we show that endogenous chemerin is abundant in human epidermis, and that inhibition of bacteria growth by exudates from organ cultures of primary human skin keratinocytes is largely chemerin-dependent. Using a panel of overlapping chemerin-derived synthetic peptides, we demonstrate that the antibacterial activity of chemerin is primarily mediated by Val66-Pro85, which causes direct bacterial lysis. Therefore, chemerin is an antimicrobial agent in human skin. 相似文献
68.
69.
Benjamin Maasoumy Kerstin Port Antoaneta Angelova Markova Beatriz Calle Serrano Magdalena Rogalska-Taranta Lisa Sollik Carola Mix Janina Kirschner Michael P. Manns Heiner Wedemeyer Markus Cornberg 《PloS one》2013,8(2)
Background
HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center.Methods
All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12.Results
208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12.Conclusions
P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options. 相似文献70.
Adrie Bekker Hendrik S. Schaaf Heather R. Draper Magdalena Kriel Anneke C. Hesseling 《PloS one》2016,11(11)
BackgroundTuberculosis during pregnancy and treatment outcomes are poorly defined in high prevalence tuberculosis and HIV settings.MethodsA prospective cohort study of pregnant and postpartum women identified to be routinely on antituberculosis treatment was conducted at Tygerberg Hospital, Cape Town, South Africa, from January 2011 through December 2011. Maternal tuberculosis disease spectrum and tuberculosis-exposed newborns were characterized by maternal HIV status. Maternal tuberculosis treatment outcomes were documented and a multivariable regression model identified predictors of unfavourable tuberculosis treatment outcomes. Infant outcomes were also described.ResultsSeventy-four women with tuberculosis, 53 (72%) HIV-infected, were consecutively enrolled; 35 (47%) were diagnosed at delivery or postpartum and 22 (30%) of women reported previous antituberculosis treatment. HIV-infected women were 5.67 times more likely to have extrapulmonary tuberculosis (95% CI 1.18–27.25, p = 0.03). All 5 maternal deaths were amongst HIV-infected women. Birth outcomes were available for 75 newborns (2 sets of twins, missing data for 1 stillbirth). Of the 75 newborns, 49 (65%) were premature and 44 (59%) were low birth weight (LBW; <2500 grams). All 6 infants who died and the 4 stillbirths were born to HIV-infected women. Unfavourable tuberculosis treatment outcomes were documented in 33/74 (45%) women. Unfavourable maternal tuberculosis outcome was associated with delivery of LBW infants (OR 3.83; 95% CI 1.40–10.53, p = 0.009).ConclusionsA large number of pregnant women with tuberculosis presented at a provincial referral hospital. All maternal and infant deaths occurred in HIV-infected women and their newborns. Maternal tuberculosis treatment outcomes were poor. 相似文献