全文获取类型
收费全文 | 2490篇 |
免费 | 142篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 27篇 |
儿科学 | 80篇 |
妇产科学 | 102篇 |
基础医学 | 386篇 |
口腔科学 | 53篇 |
临床医学 | 276篇 |
内科学 | 449篇 |
皮肤病学 | 29篇 |
神经病学 | 309篇 |
特种医学 | 76篇 |
外科学 | 188篇 |
综合类 | 8篇 |
一般理论 | 2篇 |
预防医学 | 221篇 |
眼科学 | 33篇 |
药学 | 199篇 |
中国医学 | 8篇 |
肿瘤学 | 196篇 |
出版年
2024年 | 3篇 |
2023年 | 23篇 |
2022年 | 64篇 |
2021年 | 107篇 |
2020年 | 78篇 |
2019年 | 65篇 |
2018年 | 100篇 |
2017年 | 64篇 |
2016年 | 71篇 |
2015年 | 74篇 |
2014年 | 100篇 |
2013年 | 161篇 |
2012年 | 189篇 |
2011年 | 210篇 |
2010年 | 98篇 |
2009年 | 81篇 |
2008年 | 146篇 |
2007年 | 141篇 |
2006年 | 152篇 |
2005年 | 161篇 |
2004年 | 117篇 |
2003年 | 94篇 |
2002年 | 88篇 |
2001年 | 26篇 |
2000年 | 21篇 |
1999年 | 17篇 |
1998年 | 18篇 |
1997年 | 15篇 |
1996年 | 17篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1992年 | 10篇 |
1991年 | 20篇 |
1990年 | 13篇 |
1989年 | 10篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1983年 | 3篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1970年 | 4篇 |
1967年 | 2篇 |
排序方式: 共有2642条查询结果,搜索用时 15 毫秒
1.
Katalin Vehmeyer Tibor Hajto Katarina Hostanska Stefan Knemann Holger Lser Reinhard Saller Bernhard Wrmann 《European journal of haematology》1998,60(1):16-20
Abstract: The galactoside-specific plant lectin, Viscum album agglutinin (VAA-I) increases cellular parameters of natural host defence. It also binds to a variety of haematopoietic cells, including progenitors. We investigated whether VAA-I has a stimulatory effect on haematopoietic progenitor cells. Peripheral blood progenitor cells from 7 healthy volunteers were cultured in a colony assay with VAA-I plus erythropoietin (EPO) and stem cell factor (SCF). At 50 pg/ml VAA-I induced a significant increase in the cytokine-dependent clonogenic growth (52% in median, p<0.05). In another set of experiments purified CD34+ cells were isolated from the bone marrow aspirate of 4 patients with non-metastatic breast cancer using fluorescence-activated cell sorting. Binding to CD34+ cells was demonstrated by using directly fluorescence-conjugated VAA-I. Co-incubation with d -galactose significantly abrogated this effect. CD34+ cells were cultured in the presence of EPO, SCF, interleukin-3, granulocyte/monocyte colony-stimulating factor and granulocyte colony-stimulating factor. VAA-I alone had no measurable effect on the clonogenic growth of the isolated cells. However, at concentrations of 100 and 250 pg/ml VAA-I increased the cytokine-dependent proliferation and differentiation of CD34+ cells by a median of 75 and 85%, respectively. The results show that VAA-I binds to haematopoietic progenitor cells and has a co-stimulatory effect on their proliferation. 相似文献
2.
Katarina M?rtensson Dionisios Chrysis Lars S?vendahl 《Journal of bone and mineral research》2004,19(11):1805-1812
We hypothesized that pro-inflammatory cytokines can act locally in the growth plate to impair longitudinal growth. In a model of cultured fetal rat metatarsal bones, we found that IL-1beta and TNF-alpha act in synergy to inhibit longitudinal growth, an effect linked to decreased proliferation and increased apoptosis of growth plate chondrocytes. IGF-I could partially reverse all these effects. INTRODUCTION: Children with chronic inflammatory conditions, such as Crohn's disease or rheumatoid arthritis, experience impaired longitudinal growth. The inflammatory process itself, which includes upregulation of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha, is believed to be at least partly responsible for the poor growth in these patients. This study aimed to clarify whether these cytokines can act locally in the growth plate to suppress longitudinal growth and whether any negative effects can be reversed by insulin-like growth factor-I (IGF-I). MATERIALS AND METHODS: The effects of cytokines on longitudinal bone growth were studied in fetal (day E20) rat metatarsal bones kept in culture. After a 7-day culture, the bones were sectioned, and chondrocyte proliferation was assessed by bromodeoxyuridine (BrdU) incorporation and apoptosis by TUNEL. RESULTS: When added separately, IL-1beta and TNF-alpha impaired longitudinal bone growth only at a high concentration (100 ng/ml each; p < 0.05 versus control). In contrast, when added in combination, IL-1beta and TNF-alpha potently inhibited growth at far lower concentrations (from 3 ng/ml each; p < 0.001 versus control) and also decreased chondrocyte proliferation and increased apoptosis. Growth failure induced by the combination of IL-1beta and TNF-alpha (10 ng/ml each) could be counteracted by anti-IL-1beta (100 ng/ml; p < 0.001), anti-TNF-alpha (100 ng/ml; p < 0.001), or IGF-I (100 ng/ml; p < 0.01). IL-6 did not affect longitudinal growth even when added in combination with IL-1beta or TNF-alpha (10 ng/ml each). CONCLUSIONS: We show that IL-1beta and TNF-alpha act in synergy to locally suppress longitudinal growth, an effect that can be partially reversed by IGF-I. Although growth hormone (GH)/IGF-I may improve longitudinal growth in children with chronic inflammatory diseases, our results suggest that the inflammatory process itself must be targeted to achieve normal growth. 相似文献
3.
4.
Mutant Quaking mice (C57BL/6J) display convulsive tonic-clonic seizures that can be either spontaneous or triggered by manipulation of the animal or by auditory stimulation. Several abnormalities have been found (especially in the noradrenergic system) in the brainstem of this mutant strain. We first verified by electrophysiological recording that the cerebral cortex was not involved in the generation or in the development of these fits. Then we showed that tonic-clonic seizures similar to those obtained in the freely moving animal were triggered by low-threshold (LT, 5-50 microA) or high-threshold (HT, 55-150 microA) stimuli performed during head restraint. LT stimuli were mostly efficient in a number of ponto-bulbar and mesencephalic structures, including several reticular nuclei, the locus coeruleus, the nucleus subcoeruleus and the red nucleus, whereas HT stimuli were generally necessary to trigger fits by stimulating the nuclei pontis, the substantia nigra, the central gray area and the cerebellar nuclei. Seizures were also provoked at the diencephalic level with LT stimulation delivered in the medial thalamic area, the nucleus reticularis thalami and some subthalamic regions (zona incerta, H field of Forel). In contrast, no fits were obtained by stimulating the cerebellar cortex and the inferior colliculus, the ventral and lateral groups of thalamic nuclei or the telencephalic regions (hippocampus, amygdala, caudate nucleus, putamen and cerebral cortex), with the exception of the globus pallidus. 相似文献
5.
Viktoria Werkström Lars Ny Katarina Persson K.-E. Andersson 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):151-158
Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field
stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory
control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We
investigated the functional and morphological effects of α-latrotoxin (αLTX), a spider neurotoxin believed to cause massive
release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared
to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor Nω-nitro-L-arginine (L-NOARG: 0.3 mM) both αLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine,
no contraction was observed, and under these conditions αLTX and EFS induced relaxation. At low frequencies (<12 Hz), the
EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first
phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first
phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 μM ω-conotoxin GVIA,
blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence
of L-NOARG or ω-conotoxin GVIA, the αLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and
ω-conotoxin GVIA further reduced or abolished the relaxation. In preparationstreated with tetrodotoxin or scorpion venom,
believed to inactivate nerves by acting on sodium channels, αLTX and EFS had no effects. αLTX-induced relaxation was not associated
with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation.
A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation
was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and ω-conotoxin GVIA. Ultrastructural
analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle.
In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. αLTX caused
a major loss of both types of vesicle. The present data suggest that αLTX has the ability to release not only adrenergic and
cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra.
Received: 13 January 1997 / Accepted: 17 April 1997 相似文献
6.
Francisco Fierro Katarina Kosalková Santiago Gutiérrez Juan F. Martín 《Current genetics》1996,29(5):482-489
Plasmid vectors containing theAMA1 sequence transformed with high efficiency and replicated autonomously inPenicillium chrysogenum. The efficiency of transformation ofP. chrysogenum was related to the length of theAMA1 fragment used for constructing the different autonomously replicating plasmids. One of the two palindromic inverted repeats ofAMA1 (the 2.2-kbSalI-HindIII fragment) is sufficient to confer autonomous replication and a high transformation efficiency. Deletion of the 0.6-kb central fragment located between the inverted repeats did not affect either the ability of the plasmids to replicate autonomously or the efficiency of transformation, but did alter the mitotic stability and the plasmid copy number. Deletion of any fragment of the 2.2-kb repeat caused the loss of the ability to replicate autonomously and reduced the transformation efficiency. Most of the transformants retained the original plasmid configuration, as multimers and without reorganization, after several rounds of autonomous replication. TheAMA1 region works as an origin of replication inP. chrysogenum andA. nidulans but not apparently inAcremonium chrysogenum. 相似文献
7.
8.
Gunilla Caisander Hannah Park Katarina Frej Jenny Lindqvist Christina Bergh Kersti Lundin Charles Hanson 《Chromosome research》2006,14(2):131-137
There have been recent reports of human embryonic stem cell (hESC) lines developing chromosomal aberrations after long-term
culture, indicating an unstable genomic status due to the in vitro milieu. This raises concern, since it would limit their use in therapeutics. In this study the chromosomal status of five
well-characterized hESC lines, SA002, SA002.5, AS034.1.1, SA121 and SA461, was monitored during long-term in vitro culture. The criteria of defined hESCs were met by all of the five hESC lines (four diploid and one trisomic for chromosome
13). The genomes were screened for chromosomal aberrations and rearrangements using comparative genomic hybridization (CGH),
interphase fluorescence in situ hybridization (FISH) and traditional karyotyping on several occasions while in culture. The genomic integrity was shown to
be maintained after repeated freeze-thaw procedures and continuous culture in vitro for up to 22 months (148 passages). We discuss the most common de novo chromosomal aberrations reported in hESCs, as well as their possible origin. 相似文献
9.
Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V 总被引:1,自引:2,他引:1
Bahram Mohammadi Nenad Mitrovic Frank Lehmann-Horn Reinhard Dengler Johannes Bufler 《The Journal of physiology》2003,547(3):691-698
Missense mutations of the human skeletal muscle voltage-gated Na+ channel (hSkM1) cause a variety of neuromuscular disorders. The mutation R1448H results in paramyotonia congenita and causes cold-induced myotonia with subsequent paralysis. The mutation M1360V causes an overlapping syndrome with both K+ -induced muscle weakness and cold-induced myotonia. The molecular mechanisms of the temperature dependence of these disorders are not well understood. Therefore we investigated physiological parameters of these Na+ channel mutations at different temperatures. Channel proteins were recombinantly expressed in human embryonic kidney cells and studied electrophysiologically, using the whole-cell patch-clamp technique. We compared the wild-type (WT) channel with both mutants at different temperatures. Both mutations had slower inactivation and faster recovery from inactivation compared to WT channels. This effect was more pronounced at the R1448H mutation, leading to a larger depolarization of the cell membrane causing myotonia and paralysis. The voltage dependence of activation of R1448H was shifted to more negative membrane potentials at lower temperature but not at the M1360V mutation or in the WT. The window current by mutation R1448H was increased at lower temperatures. The results of this study may explain the stronger cold-induced clinical symptoms resulting from the R1448H mutation in contrast to the M1360V mutation. 相似文献
10.
Olle Ringdén Marie Schaffer Katarina Le Blanc Ulla Persson Dan Hauzenberger Mohammad R Abedi Olle Olerup Per Ljungman Mats Remberger 《Biology of blood and marrow transplantation》2004,10(2):128-134
The aim of this study was to identify significant prognostic factors by using unrelated genomically HLA-A, -B and -DRB1-identical donors. Such data could help to choose the best donor. We studied 136 consecutive patients with hematologic malignancies and a median age of 32 years (range, 0-55 years) who received hematopoietic stem cell transplantation. Bone marrow grafts were given to 83 and peripheral blood stem cells to 53 patients. The cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 30% and of chronic GVHD was 54%. At 5 years, the overall transplant-related mortality (TRM) was 34%, and patient survival was 50%. In Cox multivariate analysis, 32 potential risk factors were analyzed. Monoclonal antibody OKT-3 during conditioning was correlated with grade II to IV acute GVHD, chronic GVHD, and TRM. HLA-DP mismatch was associated with poor TRM and poor survival. Cytomegalovirus-seropositive patients with a seronegative donor had a decreased leukemia-free survival. Five-year TRM was 14% with no risk factor, 38% with 1 risk factor, and 87% with 2 risk factors. The 5-year survival was 72%, 48%, and 30% with 0, 1, and 2 risk factors, respectively. We concluded that unrelated hematopoietic stem cell transplantation may be improved if an optimal donor and immunosuppression are chosen. 相似文献