全文获取类型
收费全文 | 13863篇 |
免费 | 1114篇 |
国内免费 | 73篇 |
学科分类
医药卫生 | 15050篇 |
出版年
2024年 | 15篇 |
2023年 | 132篇 |
2022年 | 108篇 |
2021年 | 647篇 |
2020年 | 350篇 |
2019年 | 452篇 |
2018年 | 514篇 |
2017年 | 404篇 |
2016年 | 452篇 |
2015年 | 489篇 |
2014年 | 604篇 |
2013年 | 743篇 |
2012年 | 1140篇 |
2011年 | 1223篇 |
2010年 | 680篇 |
2009年 | 556篇 |
2008年 | 873篇 |
2007年 | 920篇 |
2006年 | 809篇 |
2005年 | 797篇 |
2004年 | 739篇 |
2003年 | 606篇 |
2002年 | 602篇 |
2001年 | 122篇 |
2000年 | 92篇 |
1999年 | 106篇 |
1998年 | 117篇 |
1997年 | 110篇 |
1996年 | 75篇 |
1995年 | 74篇 |
1994年 | 54篇 |
1993年 | 41篇 |
1992年 | 45篇 |
1991年 | 43篇 |
1990年 | 39篇 |
1989年 | 22篇 |
1988年 | 26篇 |
1987年 | 17篇 |
1986年 | 22篇 |
1985年 | 29篇 |
1984年 | 16篇 |
1983年 | 22篇 |
1982年 | 13篇 |
1981年 | 13篇 |
1979年 | 10篇 |
1978年 | 12篇 |
1977年 | 8篇 |
1974年 | 9篇 |
1971年 | 7篇 |
1966年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Glial cell expression of hepatocyte growth factor in vitreoretinal proliferative disease 总被引:5,自引:0,他引:5
Hollborn M Krausse C Iandiev I Yafai Y Tenckhoff S Bigl M Schnurrbusch UE Limb GA Reichenbach A Kohen L Wolf S Wiedemann P Bringmann A 《Laboratory investigation; a journal of technical methods and pathology》2004,84(8):963-972
The hepatocyte growth factor (HGF) has been crucially implicated in the development of proliferative retinal diseases; however, it is unclear whether retinal glial cells express or respond to HGF. Therefore, we examined the expression of HGF and of the receptor for HGF, c-Met, by immunohistochemical costaining with glial fibrillary acidic protein (GFAP) in epiretinal membranes of patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), respectively. Furthermore, it was determined whether cells of the human retinal glial cell line, MIO-M1, secrete HGF protein, and whether HGF stimulates proliferation and chemotaxis, and secretion of the vascular endothelial growth factor (VEGF). Neuroretinas of patients with PVR express elevated mRNA level for HGF in comparison to control retinas. In epiretinal membranes of patients with PVR or PDR, immunoreactivity for HGF and for c-Met, respectively, partially colocalized with immunoreactivity for GFAP. Fetal bovine serum and basic fibroblast growth factor, but not heparin-binding epidermal or platelet-derived growth factors, evoked HGF secretion by cultured retinal glial cells. HGF displayed only a marginal effect on cell proliferation while it stimulated chemotaxis. HGF promoted the secretion of VEGF, via activation of the phosphatidylinositol-3 kinase. It is concluded that glial cells in epiretinal membranes express both HGF protein and c-Met receptors. The results suggest an autocrine/paracrine role of HGF in glial cell responses during proliferative vitreoretinal disorders as well as in retinal neovascularization, by stimulating of VEGF release. 相似文献
52.
Tezak Z Prandini P Boscaro M Marin A Devaney J Marino M Fanin M Trevisan CP Park J Tyson W Finkel R Garcia C Angelini C Hoffman EP Pegoraro E 《Human mutation》2003,21(2):103-111
Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients. 相似文献
53.
Hamvas RM Johnson M Vlieger AM Ling C Sherriff A Wade A Klein NJ Turner MW Webster AD 《Infection and immunity》2005,73(8):5238-5240
Polymorphisms in exon 1 of the MBL-2 gene, resulting in reduced plasma levels of mannose binding lectin, were significantly overrepresented in 23 patients with primary antibody deficiency and culture-proven mycoplasma infections (P = 0.0038). This association persisted with the inclusion of a further nine suspected (doxycycline-responsive) cases (P = 0.0087). The lectin was shown to bind to three strains of mycoplasma. 相似文献
54.
Guarner J Jernigan JA Shieh WJ Tatti K Flannagan LM Stephens DS Popovic T Ashford DA Perkins BA Zaki SR;Inhalational Anthrax Pathology Working Group 《The American journal of pathology》2003,163(2):701-709
During October and November 2001, public health authorities investigated 11 patients with inhalational anthrax related to a bioterrorism attack in the United States. Formalin-fixed samples from 8 patients were available for pathological and immunohistochemical (IHC) study using monoclonal antibodies against the Bacillus anthracis cell wall and capsule. Prominent serosanguinous pleural effusions and hemorrhagic mediastinitis were found in 5 patients who died. Pulmonary infiltrates seen on chest radiographs corresponded to intraalveolar edema and hyaline membranes. IHC assays demonstrated abundant intra- and extracellular bacilli, bacillary fragments, and granular antigen-staining in mediastinal lymph nodes, surrounding soft tissues, and pleura. IHC staining in lung, liver, spleen, and intestine was present primarily inside blood vessels and sinusoids. Gram's staining of tissues was not consistently positive. In 3 surviving patients, IHC of pleural samples demonstrated abundant granular antigen-staining and rare bacilli while transbronchial biopsies showed granular antigen-staining in interstitial cells. In surviving patients, bacilli were not observed with gram's stains. Pathological and IHC studies of patients who died of bioterrorism-related inhalational anthrax confirmed the route of infection. IHC was indispensable for diagnosis of surviving anthrax cases. The presence of B. anthracis antigens in the pleurae could explain the prominent and persistent hemorrhagic pleural effusions. 相似文献
55.
Role of surface-exposed loops of Haemophilus influenzae protein P2 in the mitogen-activated protein kinase cascade 下载免费PDF全文
Galdiero S Capasso D Vitiello M D'Isanto M Pedone C Galdiero M 《Infection and immunity》2003,71(5):2798-2809
The outer membrane of gram-negative bacteria contains several proteins, and some of these proteins, the porins, have numerous biological functions in the interaction with the host; porins are involved in the activation of signal transduction pathways and, in particular, in the activation of the Raf/MEK1-MEK2/mitogen-activated protein kinase (MAPK) cascade. The P2 porin is the most abundant outer membrane protein of Haemophilus influenzae type b. A three-dimensional structural model for P2 was constructed based on the crystal structures of Klebsiella pneumoniae OmpK36 and Escherichia coli PhoE and OmpF. The protein was readily assembled into the beta-barrel fold characteristic of porins, despite the low sequence identity with the template proteins. The model provides information on the structural features of P2 and insights relevant for prediction of domains corresponding to surface-exposed loops, which could be involved in the activation of signal transduction pathways. To identify the role of surface-exposed loops, a set of synthetic peptides were synthesized according to the proposed model and were assayed for MEK1-MEK2/MAPK pathway activation. Our results show that synthetic peptides corresponding to surface loops of protein P2 are able to activate the MEK1-MEK2/MAPK pathways like the entire protein, while peptides modeled on internal beta strands are unable to induce significant phosphorylation of the MEK1-MEK2/MAPK pathways. In particular, the peptides corresponding to loops L5 (Lys206 to Gly219), L6B (Ser239 to Lys253), and L7 (Thr280 to Lys287) activate, as the whole protein, essentially JNK and p38. 相似文献
56.
Charlotte Charpentier Didier Laureillard Mustapha Sodqi Ali Si-Mohamed Marina Karmochkine Laurent Bélec Laurence Weiss Christophe Piketty 《Journal of clinical virology》2008,43(2):212-215
BACKGROUND: Salvage therapy based on foscarnet plus a thymidine analog is effective in patients with advanced-stage HIV disease and viruses harbouring multiple drug-resistance mutations. OBJECTIVE: To identify viral genetic determinants associated with the virological efficacy of foscarnet salvage therapy. STUDY DESIGN: Thirteen patients received foscarnet at a fixed dose of 80mg/kg twice daily for 14 days, in combination with zidovudine or stavudine. RESULTS: The baseline median HIV viral load and CD4 cell count were 5.10log(10)copies/ml and 23cells/mm(3), respectively. Following foscarnet therapy, viral load fell by a median of 1.84log(10)copies/ml (range: -0.29 to -2.82), and by at least 1log(10)copies/ml in 11 patients, all of whom harboured viruses with at least three thymidine-associated mutations (TAMs). The two patients with smaller declines in viral load (<0.50log(10)copies/ml) harboured viruses with only one or zero TAMs. CONCLUSIONS: These findings corroborate, in vivo, the impact of TAMs on HIV susceptibility to foscarnet. The virological response to foscarnet salvage therapy in multiclass-experienced patients may thus differ according to the number of TAMs. 相似文献
57.
Marina A. Noordegraaf Gert Jan Kuiper Antonius T. M. Marcelis Ernst J. R. Sudhlter 《Macromolecular chemistry and physics.》1997,198(11):3681-3697
A new series of rigid polymers was synthesized via radical copolymerization of N-phenylmaleimides, bearing pendant chromophores, with 4-vinylpyridine or styrene. Structural characterization was achieved by 1H NMR and 13C NMR spectroscopy, gel permeation chromatography (GPC), elemental analysis and differential scanning calorimetry (DSC). The thermal properties as well as the morphology of the investigated polymers at the air-water interface appear to be related to their rigidity. In spite of the presence of excellent mesogenic units, the polymers do not exhibit liquid crystalline behaviour. The 4-vinylpyridine copolymers form stable monolayers at the air-water interface. The attached chromophores electronically behave as monomers, as shown with in situ UVVIS absorption spectroscopy. Brewster angle microscopy shows a spontaneous aggregation of these polymers into domains on a neutral subphase, whereas on an acidic subphase a more homogeneous monolayer is formed. The monolayers give Z-type transfer onto hydrophilic quartz. However, the chromophores seem to be oriented randomly at the substrate surface. The styrene copolymers do not form stable monolayers as a result of crystallization at the air-water interface. 相似文献
58.
Dejan Popovic Tessa Gordon Victor F. Rafuse Dr. Arthur Prochazka 《Annals of biomedical engineering》1991,19(3):303-316
Implanted wire electrodes are increasingly being used for the functional electrical stimulation of muscles in partially paralysed
patients, yet many of their basic characteristics are poorly understood. In this study we investigated the selectivity, recruitment
characteristics and range of control of several types of electrode in triceps surae and plantaris muscles of anaesthetized
cats. We found that nerve cuffs are more efficient and selective (i.e., cause less stimulus spread to surrounding muscles)
than intramuscular electrodes. Bipolar intramuscular stimulation was more efficient and selective than monopolar stimulation,
but only if the nerve entry point was between the electrodes. Monopolar electrodes are efficient and selective if located
close to the nerve entry point, but their performance declines with distance from it. Nonetheless, for a variety of reasons
monopolar stimulation provides the best compromise in many current applications. Short duration pulses offer the best efficiency
(least charge per pulse to elicit force) but high peak currents, increasing the risk of electrode corrosion and tissue damage.
Electrode size has little effect on recruitment and should therefore be maximised because this minimises current density. 相似文献
59.
Two members of the ADAM (a disintegrin and metalloprotease)-family, MADDAM and decysin, were described as dendritic cell (DC) maturation markers. We are interested in monocyte differentiation and investigated in particular the expression pattern of both genes during the differentiation of human monocytes into DC and macrophages (MAC). Both genes are weakly expressed in freshly isolated monocytes. In immature DC decysin mRNA was absent, even after induction of the terminal differentiation of DC by CD40L or tumour necrosis factor-alpha (TNF-alpha). Only in DC maturated by lipopolysaccharide (LPS) strong signals of decysin mRNA were detected. However, MADDAM mRNA was expressed in immature DC and the expression was markedly increased after induction of the terminal DC differentiation by various stimuli. In contrast, MAC showed a high constitutive decysin mRNA expression, but expressed no MADDAM mRNA. On protein level similar results of MADDAM expression were obtained. Stimulation of MAC by LPS did not induce MADDAM mRNA expression, while decysin mRNA expression was strongly increased. Further investigations revealed that the well-known inducer of MAC differentiation, 1alpha,25-dihydroxyvitamin D3 up-regulated decysin mRNA expression during the differentiation of primary monocytes and myelomonocytic THP-1 cells into MAC. In vivo decysin mRNA expression was only detected in human colon, but not in other tissues we examined. Accordingly, isolated intestinal MAC expressed decysin mRNA. In conclusion, decysin and MADDAM mRNA expression were regulated in an opposite way during monocyte differentiation: MADDAM mRNA and protein was mainly detected in DC, whereas decysin mRNA expression was mainly found in MAC. Therefore only MADDAM, but not decysin is a suitable marker for human monocyte-derived DC. 相似文献
60.