全文获取类型
收费全文 | 2354篇 |
免费 | 125篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 70篇 |
儿科学 | 50篇 |
妇产科学 | 90篇 |
基础医学 | 421篇 |
口腔科学 | 44篇 |
临床医学 | 190篇 |
内科学 | 640篇 |
皮肤病学 | 59篇 |
神经病学 | 165篇 |
特种医学 | 31篇 |
外科学 | 269篇 |
综合类 | 10篇 |
预防医学 | 111篇 |
眼科学 | 67篇 |
药学 | 183篇 |
中国医学 | 7篇 |
肿瘤学 | 82篇 |
出版年
2023年 | 19篇 |
2022年 | 66篇 |
2021年 | 151篇 |
2020年 | 50篇 |
2019年 | 55篇 |
2018年 | 71篇 |
2017年 | 61篇 |
2016年 | 59篇 |
2015年 | 58篇 |
2014年 | 90篇 |
2013年 | 104篇 |
2012年 | 186篇 |
2011年 | 185篇 |
2010年 | 102篇 |
2009年 | 66篇 |
2008年 | 152篇 |
2007年 | 174篇 |
2006年 | 142篇 |
2005年 | 133篇 |
2004年 | 116篇 |
2003年 | 136篇 |
2002年 | 106篇 |
2001年 | 13篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1938年 | 3篇 |
1933年 | 5篇 |
1932年 | 5篇 |
1929年 | 4篇 |
1928年 | 4篇 |
1926年 | 7篇 |
1922年 | 3篇 |
1914年 | 3篇 |
1913年 | 7篇 |
1912年 | 6篇 |
1910年 | 3篇 |
1908年 | 4篇 |
排序方式: 共有2489条查询结果,搜索用时 15 毫秒
11.
12.
Human heat shock protein 60 (409-424) fragment is recognized by serum antibodies of patients with acute coronary syndromes. 总被引:7,自引:0,他引:7
Jan Wysocki Bozena Karawajczyk Jacek Górski Artur Korzeniowski Zbigniew Ma?kiewicz Gotfryd Kupryszewski Renata Glo?nicka 《Cardiovascular pathology》2002,11(4):238-243
Acute coronary syndromes (ACS), including unstable angina (UA) and acute myocardial infarction (MI), are clinical manifestations of a progressive atherosclerotic process. Antibodies (Ab) to heat shock proteins (hsp) have been reported to be associated with atherosclerosis. Blood samples from 35 patients with ACS and 20 healthy volunteers were tested for Ab to human hsp60 by an enzyme-linked immunosorbent assay (ELISA). Levels of specific serum Ab against hsp60 were significantly elevated in patients with ACS when compared to clinically healthy subjects. To determine the antigenic determinants recognized by these Ab, antibody binding to seven peptides, selected from the hydrophilic and acrophilic regions of the human hsp60 molecule, was assessed. Despite the individual variation in the immune response among patients, one immunodominant region was revealed corresponding to the hsp60 (409-424) peptide. The identification of this epitope may be important for understanding the function of this protein in the atherosclerotic process. 相似文献
13.
Cideciyan AV Aleman TS Swider M Schwartz SB Steinberg JD Brucker AJ Maguire AM Bennett J Stone EM Jacobson SG 《Human molecular genetics》2004,13(5):525-534
Mutations in ABCA4, which encodes a photoreceptor specific ATP-binding cassette transporter (ABCR), cause autosomal recessive forms of human blindness due to retinal degeneration (RD) including Stargardt disease. The exact disease sequence leading to photoreceptor and vision loss in ABCA4-RD is not known. Extrapolation from murine and in vitro studies predicts that two of the earliest pathophysiological features resulting from disturbed ABCR function in man would be slowed kinetics of the retinoid cycle and accelerated deposition of lipofuscin in the retinal pigment epithelium (RPE). To determine the human pathogenetic sequence, we studied surrogate measures of retinoid cycle kinetics, lipofuscin accumulation, and rod and cone photoreceptor and RPE loss in ABCA4-RD patients with a wide spectrum of disease severities. There were different extents of photoreceptor/RPE loss and lipofuscin accumulation in different regions of the retina. Slowing of retinoid cycle kinetics was not present in all patients; when present, it was not homogeneous across the retina; and the extent of slowing correlated well with the degree of degeneration. The orderly relationship between these phenotypic features permitted the development of a model of disease sequence in ABCA4-RD. The model predicted lipofuscin accumulation as a key and early component of the disease expression in man, as in mice. In man, however, abnormal slowing of the rod and cone retinoid cycle occurs at later stages of the disease sequence. Knowledge of the human ABCA4 disease sequence will be critical for defining rates of progression, selecting appropriate patients and retinal locations for future therapy, and choosing appropriate treatment outcomes. 相似文献
14.
The adhesion of human leukocytes to self-assembled monolayers of well-defined surface chemistry was investigated in vitro. Polymorphonuclear (PMN) and mononuclear leukocytes were isolated from human blood by centrifugation techniques. The effect on adhesion of cell activation produced by pre-incubation of leukocytes with phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) was also studied. Gold substrates were modified by treatment with alkanethiols with three different terminal chemical groups: COOH, OH, and CH(3). After incubation with the two subpopulations of leukocytes, the monolayers were washed, treated with fixative, stained with a Giemsa method, and observed by light microscopy to quantify the number of attached leukocytes. Comparative quantification of the density of leukocyte adhesion to the three types of self-assembled monolayers was determined. The hydrophobic surface expressing CH(3) was found to be the one that induced the highest adhesion density of leukocytes, both of PMN and mononuclear cells. In vitro activation of both mononuclear and PMN leukocytes further increased cell adhesion to the chemically defined monolayers that were used. This enhancement was higher for PHA-activated than for PMA-stimulated mononuclear cells, whereas PMA treatment of neutrophils resulted in a higher rate of adhesion of these cells than PHA stimulation. 相似文献
15.
Lichtenberg A Dumlu G Walles T Maringka M Ringes-Lichtenberg S Ruhparwar A Mertsching H Haverich A 《Biomaterials》2005,26(5):555-562
Investigation of cell abilities to growth, proliferation and (de)-differentiation in a three-dimensional distribution is an important issue in biotechnological research. Here, we report the development of a new bioreactor for three-dimensional cell culture, which allows for co-cultivation of various cell types with different culture conditions in spatial separation. Preliminary results of neonatal rat cardiomyocyte cultivation are shown. Isolated neonatal rat cardiomyocytes were cultured in spatial separated bioreactor compartments in recirculating medium on a biodegradable fibrin matrix for 2 weeks. Glucose, lactate, and lactate dehydrogenase (LDH), pO2, pCO2, and pH levels were monitored in the recirculated medium, daily. Morphological characterization of matrix and cells was assessed by hematoxylin and eosin staining, and MF-20 co-immunostaining with 4',6-diamidino-2-phenylindole (DAPI). Cell viability was determined by LIVE/DEAD staining before cultivation and on day 3, 7, and 14. The optimized seeding density in the matrix was 2.0 x 10(7) cells retaining cellular proportions over the cell culture period. The bioreactor allows the maintenance of physiologic culture conditions with aerobic cell metabolism (low release of lactate, LDH), a high oxygen tension (pO2-183.7 +/- 18.4 mmHg) and physiological pH values (7.4 +/- 0.02) and a constant level of pCO2 (43.1 +/- 2.9) throughout the experimental course. The cell viability was sufficient after 2 weeks with 82 +/- 6.7% living cells. No significant differences were found between spatial separated bioreactor compartments. Our novel multifunctional bioreactor allows for a three-dimensional culture of cells with spatial separation of the co-cultured cell groups. In preliminary experiments, it provided favorable conditions for the three-dimensional cultivation of cardiomyocytes. 相似文献
16.
Inflammatory responses and cell adhesion to self-assembled monolayers of alkanethiolates on gold 总被引:1,自引:0,他引:1
The acute inflammatory response and the adhesion of cells to self-assembled monolayers (SAMs) of well-defined surface chemistry was studied in vivo using a rodent air-pouch model of inflammation. SAMs with three different terminal functional groups (OH, COOH and CH3) were implanted in subcutaneous air pouches induced in BALB/c mice. After 24 h, inflammatory cells were recovered from the air pouches and the implants were removed and prepared for observation by scanning electron microscopy (SEM). The implants coated with OH and CH3, were found to cause the highest recruitment of inflammatory cells into the subcutaneous pouches. Polymorphonuclear neutrophils (PMNs) leukocytes predominated over mononuclear cells in inflammatory exudates of SAMs-coated implants, the opposite being found in uncoated implants (controls). CH3-coated implants induced the highest number of inflammatory cells and also the largest percentage of PMNs seen in the subcutaneous pouches. Control and OH-covered implants presented the higher densities of attached inflammatory cells detected by SEM. In contrast, the CH3-coated implants showed a very low density of cells adherent to the implant surface. We conclude that the chemical nature and the degree of hydrophobicity of the surface of implants modulate both the local acute inflammatory reaction and the adhesion of leukocytes. 相似文献
17.
Krzyzak AT Jasiński A Weglarz WP Adamek D Sagnowskil P Baj M 《Acta neurobiologiae experimentalis》2005,65(3):255-264
Magnetic Resonance Diffusion Tensor Imaging (DTI) of the control and traumatic injured spinal cord of a rat in vitro is reported. Experiments were performed on excised spinal cords from 10 Wistar rats, using a home-built 6.4 T MR microscope. MRI and histopathological results were compared. Presented results show that DTI of the spinal cord, perfused with formalin 10 minutes after the injury, can detect changes in water diffusion in white matter (WM) and in gray matter (GM), in areas extending well beyond the region of direct impact. Histology of neurons of the GM shows changes that can be attributed to ischemia. This is in agreement with the observed decrease of diffusion in the injured regions, which may be attributed to the cytotoxic edema due to ischemia. However, the diffusion changes in highly anisotropic WM seem to be caused by a direct action of mechanical force of impact, which significantly distorts the nerve fibers. 相似文献
18.
Jacobson SG Sumaroka A Aleman TS Cideciyan AV Schwartz SB Roman AJ McInnes RR Sheffield VC Stone EM Swaroop A Wright AF 《Human molecular genetics》2004,13(17):1893-1902
Mutations in the nuclear receptor gene, NR2E3, cause a disorder of human retinal photoreceptor development characterized by hyperfunction and excess of the minority S (short wavelength or blue) cone photoreceptor type, but near absence of function of the majority rod receptor. NR2E3 disease can also progress to blindness. How the human retina accommodates mis-specified types and numbers of neurons and advances to retinal degeneration are unknown. We studied the retinal organization in vivo of patients with NR2E3 mutations. Early human NR2E3 disease with S cone hyperfunction showed thickened retinal layers within an otherwise normally structured retina. With visual loss, however, lamination was coarse and there was a strikingly thick and bulging appearance to the retina, localized to an annulus encircling the central fovea. This pattern was not found in other retinal degenerations. The abnormal laminar retinal architecture of early NR2E3 disease may be due in part to larger cells with an S cone phenotype in place of rods that failed to differentiate. The later-stage dysplastic appearance suggests a previously unrecognized proliferative response in human retinal degeneration. 相似文献
19.
20.
Manukyan M Triantafilou K Triantafilou M Mackie A Nilsen N Espevik T Wiesmüller KH Ulmer AJ Heine H 《European journal of immunology》2005,35(3):911-921
Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by the innate immune system. For LP, it has been shown that TLR2 is the essential receptor in cellular activation. However, molecular mechanisms of LP recognition are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (Pam(3)CSK(4)) to study the roles of CD14, TLR2 and TLR1 in binding and signaling of LP and their molecular interactions in human cells. The activity of Pam(3)CSK(4)-FLAG was TLR2 dependent, whereas the binding was enabled by CD14, as evaluated by flow cytometry and confocal microscopy. Using FRET and FRAP imaging techniques to study molecular associations, we could show that after Pam(3)CSK(4)-FLAG binding, CD14 and Pam(3)CSK(4)-FLAG associate with TLR2 and TLR1, and TLR2 is targeted to a low-mobility complex. Thus, LP binding to CD14 is the first step in the LP recognition, inducing physical proximity of CD14 and LP with TLR2/TLR1 and formation of the TLR2 signaling complex. 相似文献