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1.
Raffael Kalisch Mirjam Schubert Wolfgang Jacob Melanie S Kessler Rosa Hemauer Alexandra Wigger Rainer Landgraf Dorothee P Auer 《Neuropsychopharmacology》2006,31(5):925-932
In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior. 相似文献
2.
Thomas F Müller Dorothee Gicklhorn Therese Jungraithmayr Markus Eickmann Harald Lange Klaus Radsak Marko Reschke 《Journal of clinical virology》2002,24(1-2):45-56
The humoral immune response against human cytomegalovirus (HCMV) was evaluated in immunocompromised patients by Western blotting (WB) based on recombinant viral envelope (gB and gH) and tegument (pp150 and pp65) proteins. Three groups of patients were investigated: (a) 74 renal transplant recipients; (b) 24 hemodialysis patients, both groups without clinical evidence of viral infections; and (c) 19 renal transplant patients with manifest HCMV infections. The results obtained suggest that (i) the WB is considerably more sensitive, recognizing the HCMV-specific IgM response rather than the enzyme-linked immunosorbent assays. An IgM response was detected in one-third of all clinically asymptomatic renal patients. (ii) The virus-specific IgM response is primarily directed against the pp150 epitope. (iii) In patients with clinically manifest HCMV disease, additional IgM reactivities are most frequently directed against the glycoprotein B epitope. (iv) The severity of HCMV infections correlates with the extent of the IgM antibody response, i.e. with the number of specific epitopes involved. (v) After transplantation, IgM reactivity and its epitope-specific pattern persist for years. 相似文献
3.
Rajasekharan?Somasundaram Laura?Caputo DuPont?Guerry Dorothee?HerlynEmail author 《Journal of translational medicine》2005,3(1):41
A CD8+ cytotoxic T lymphocyte (CTL) line was derived from the peripheral blood mononuclear cells of a patient with primary melanoma.
The CD8+ CTL line specifically lysed the autologous primary melanoma cells and not the natural killer cell-sensitive K562 cells or
lymphokine activated killer cell-sensitive DAUDI cells. When a large panel of human leukocyte antigen (HLA)-matched and -unmatched
allogeneic melanoma, glioma, breast and colorectal carcinoma cells was tested as targets in cytolysis assays, 4 HLA-matched
and two HLA-unmatched allogeneic metastatic melanoma lines were lysed by the CD8+ CTL. Lysis of autologous and allogeneic melanoma cells was dependent on the effector-to-target cell ratio. Lysis of autologous
melanoma cells was not blocked by anti-HLA class I or class II antibodies, confirming that the cytolytic activity of the CD8+ CTL was HLA-unrestricted. CTL lysis of autologous melanoma cells was CD3 (T cell receptor) dependent and FAS-FAS-L, and CD1
independent. Identification of the melanoma-associated antigen recognized by the HLA-unrestricted CTL may provide a vaccine
for a broad population of melanoma patients. 相似文献
4.
Kopp MV Brauburger J Riedinger F Beischer D Ihorst G Kamin W Zielen S Bez Friedrichs F Von Berg A Gerhold K Hamelmann E Hultsch Kuehr J 《The Journal of allergy and clinical immunology》2002,110(5):728-735
BACKGROUND: Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. OBJECTIVE: We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. METHODS: Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. RESULTS: Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587 ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition, treatment with anti-IgE was also followed by significantly lower SLT releases to the allergens unrelated to SIT (grass SIT: 300 ng/L [1-2432 ng/L] in response to birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch SIT: 2792 ng/L [154-5839 ng/L], P =.04]. CONCLUSION: Anti-IgE therapy reduces leukotriene release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy independent of the type of SIT allergen used. 相似文献
5.
Klaus-Michael Debatin Dorothee Süss Peter H. Krammer 《European journal of immunology》1994,24(3):753-758
Negative selection during T cell ontogeny involves selective induction of apoptosis in thymocytes. In peripheral lymphoid cells, apoptosis may be mediated via the APO-1 pathway. Here we report that APO-1 is constitutively expressed on the vast majority of human thymocytes but down-regulated at a mature stage of thymocyte development (TCRhi). This stage of development is characterized by CD28hi, CD44hi, CD69hi and up-regulation of Bcl-2 protein. We define a new thymocyte subpopulation that expresses high levels of APO-1 and intermediate levels of T cell receptor α/β (TCRim/APO-1hi). The TCRim/APO-1hi population contains a large fraction of dead cells, suggesting that the APO-1 pathway may be involved in negative selection of at least a fraction of thymocytes after intrathymic activation. 相似文献
6.
Mg2+-extrusion from Mg2+-loaded neurons of the leech, Hirudo medicinalis, is mediated mainly by Na+/Mg2+ antiport. However, in a number of leech neurons, Mg2+ is extruded in the nominal absence of extracellular Na+, indicating the existence of an additional, Na+-independent Mg2+ transport mechanism. This mechanism was investigated using electrophysiological and microfluorimetrical techniques. The rate of Na+-independent Mg2+ extrusion from Mg2+-loaded leech neurons was found to be independent of extracellular Ca2+, K+, NO3-, HCO3-, SO4(2-), HPO4(2-), and of intra- and extracellular pH. Na+-independent Mg2+ extrusion was not inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), furosemide, ouabain, vanadate, iodoacetate, 4-amino-hippurate, or alpha-cyano-4-hydroxycinnamate and was not influenced by changes in the membrane potential in voltage-clamp experiments. Na+-independent Mg2+ extrusion was, however, inhibited by the application of 2 mM probenecid, a blocker of organic anion transporters, suggesting that Mg2+ might be co-transported with organic anions. Extracellularly, of all organic anions tested (malate, citrate, lactate, alpha-ketoglutarate, and 4-amino-hippurate) only high, but physiological, concentrations of malate (30 mM) had a significant inhibitory effect on Na+-independent Mg2+ extrusion. Intracellularly, iontophoretically injected malate, citrate, or fura-2, but not Cl-, alpha-ketoglutarate, glutamate, succinate, or urate, were stimulating Na+-independent Mg2+ extrusion from those neurons that initially did not extrude Mg2+ in Na+-free solutions. Our data indicate that Mg2+ is co-transported with organic anions, preferably with malate, the predominant extracellular anion in the leech. The proposed model implies that, under experimental conditions, malate drives Mg2+ extrusion, whereas under physiological conditions, malate is actively taken up, driven by Mg2+, so that malate can be metabolized. 相似文献
7.
Miksch S Lumsden A Guenther UP Foernzler D Christen-Zäch S Daugherty C Ramesar RK Lebwohl M Hohl D Neldner KH Lindpaintner K Richards RI Struk B 《Human mutation》2005,26(3):235-248
Pseudoxanthoma elasticum (PXE) is a systemic heritable disorder that affects the elastic tissue in the skin, eye, and cardiovascular system. Mutations in the ABCC6 gene cause PXE. We performed a mutation screen in ABCC6 using haplotype analysis in conjunction with direct sequencing to achieve a mutation detection rate of 97%. This screen consisted of 170 PXE chromosomes in 81 families, and detected 59 distinct mutations (32 missense, eight nonsense, and six likely splice-site point mutations; one small insertion; and seven small and five large deletions). Forty-three of these mutations are novel variants, which increases the total number of PXE mutations to 121. While most mutations are rare, three nonsense mutations, a splice donor site mutation, and the large deletion comprising exons 23-29 (c.2996_4208del) were identified as relatively frequent PXE mutations at 26%, 5%, 3.5%, 3%, and 11%, respectively. Chromosomal haplotyping with two proximal and two distal polymorphic markers flanking ABCC6 demonstrated that most chromosomes that carry these relatively frequent PXE mutations have related haplotypes specific for these mutations, which suggests that these chromosomes originate from single founder mutations. The types of mutations found support loss-of-function as the molecular mechanism for the PXE phenotype. In 76 of the 81 families, the affected individuals were either homozygous for the same mutation or compound heterozygous for two mutations. In the remaining five families with one uncovered mutation, affected showed allelic compound heterozygosity for the cosegregating PXE haplotype. This demonstrates pseudo-dominance as the relevant inheritance mechanism, since disease transmission to the next generation always requires one mutant allelic variant from each parent. In contrast to other previous clinical and molecular claims, our results show evidence only for recessive PXE. This has profound consequences for the genetic counseling of families with PXE. 相似文献
8.
Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease 总被引:3,自引:0,他引:3
Mild cognitive impairment (MCI) defines a group of otherwise healthy elderly subjects with a markedly elevated risk of developing Alzheimer's disease (AD). In the search for biomarkers of MCI, we assessed whether MCI shares neurochemical abnormalities with AD in areas affected early in the course of the disease. As a secondary study aim, we tested to what extent neurochemical findings reflect neuropsychological deficits. Proton spectroscopy was performed in 19 MCI patients, 18 AD patients and 22 age and gender matched controls (CON) within the parietal gray and white matter (PWM and PGM) and the hippocampus (HIP). The cognitive test battery used included measures compiled by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The N-acetyl-aspartate to creatine ratio (NAA/Cr) was significantly reduced in the HIP of MCI and AD compared with CON (p < 0.05). Only AD patients showed parietal abnormalities, namely significantly elevated myoinositol (mI/Cr and mI/NAA) in PGM, reduced NAA/Cr and elevated mI/NAA in PWM. MCI subjects were significantly impaired in categorical verbal fluency (VF) (p < 0.001) and delayed verbal recall (DVR) (p < 0.001). VF was positively correlated with hippocampal NAA/Cr (p < 0.05) and parietal mI/NAA (p < 0.05). In summary, this study demonstrates shared neurobiological hippocampal abnormalities in MCI and AD, whereas parietal lobe neurochemical profiles and functions were normal in MCI. Thus, biological evidence is provided that MCI represents a precursor stage of AD. Moreover, multivoxel 1H MRS may enable an objective staging of the neurodegenerative process underlying the age-dependent cognitive deficits eventually leading to dementia. 相似文献
9.
Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility. 总被引:6,自引:0,他引:6
Sabine Gesierich Claudia Paret Dagmar Hildebrand Jürgen Weitz Kaspar Zgraggen Friedrich H Schmitz-Winnenthal Vaclav Horejsi Osamu Yoshie Dorothee Herlyn Leonie K Ashman Margot Z?ller 《Clinical cancer research》2005,11(8):2840-2852
PURPOSE: Patients with pancreatic adenocarcinoma have a poor prognosis due to the extraordinary high invasive capacity of this tumor. Altered integrin and tetraspanin expression is suggested to be an important factor. We recently reported that after protein kinase C activation, colocalization of alpha6beta4 with the tetraspanin CO-029 strongly supports migration of a rat pancreatic adenocarcinoma. The finding led us to explore whether and which integrin-tetraspanin complexes influence the motility of human pancreatic tumors. EXPERIMENTAL DESIGN: Integrin and tetraspanin expression of pancreatic and colorectal adenocarcinoma was evaluated with emphasis on colocalization and the impact of integrin-tetraspanin associations on tumor cell motility. RESULTS: The majority of pancreatic and colorectal tumors expressed the alpha2, alpha3, alpha6, beta1, and beta4 integrins and the tetraspanins CD9, CD63, CD81, CD151, and CO-029. Expression of alpha6beta4 and CO-029 was restricted to tumor cells, whereas alpha1, alpha2, alpha3, alpha6, beta1, and CD9, CD81, CD151 were also expressed by the surrounding stroma. CD63, CD81, and beta1 expression was observed at comparably high levels in healthy pancreatic tissue. alpha3beta1 frequently colocalized and coimmunoprecipitated with CD9, CD81, and CD151, whereas alpha6beta4 colocalized and coimmunoprecipitated mostly with CD151 and CO-029. Notably, protein kinase C activation strengthened only the colocalization of CD151 and CO-029 with beta4 and was accompanied by internalization of the integrin-tetraspanin complex, decreased laminin 5 adhesion, and increased cell migration. CONCLUSION: alpha6beta4 is selectively up-regulated in pancreatic and colorectal cancer. The association of alpha6beta4 with CD151 and CO-029 correlates with increased tumor cell motility. 相似文献
10.
Dorothee Bienzle Joyce Rousseau David Marom Jennifer MacNicol Linda Jacobson Stephanie Sparling Natalie Prystajecky Erin Fraser J. Scott Weese 《Emerging infectious diseases》2022,28(6):1154
We tested swab specimens from pets in households in Ontario, Canada, with human COVID-19 cases by quantitative PCR for SARS-CoV-2 and surveyed pet owners for risk factors associated with infection and seropositivity. We tested serum samples for spike protein IgG and IgM in household pets and also in animals from shelters and low-cost neuter clinics. Among household pets, 2% (1/49) of swab specimens from dogs and 7.7% (5/65) from cats were PCR positive, but 41% of dog serum samples and 52% of cat serum samples were positive for SARS-CoV-2 IgG or IgM. The likelihood of SARS-CoV-2 seropositivity in pet samples was higher for cats but not dogs that slept on owners’ beds and for dogs and cats that contracted a new illness. Seropositivity in neuter-clinic samples was 16% (35/221); in shelter samples, 9.3% (7/75). Our findings indicate a high likelihood for pets in households of humans with COVID-19 to seroconvert and become ill. 相似文献