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31.
Shigemitsu Iwai MD Kei Torikai MD Chris M. Coppin MD Yoshiki Sawa MD 《Journal of artificial organs》2007,10(1):29-35
Currently used bioprosthetic valves have several limitations such as calcification and functional deterioration, and revitalization
through cellular ingrowth is impossible. To overcome these obstacles, we have developed a minimally immunogenic tissue-engineered
valve that consists of an unfixed, decellularized porcine valve scaffold capable of being spontaneously revitalized in vivo
after implantation. Porcine aortic root tissue was decellularized using detergents such as sodium lauryl sulfate and Triton
X-100. The porcine valve was treated very gently and plenty of time was allowed for constituents to diffuse in and out of
the matrix. In a preliminary study, a piece of decellularized porcine valve tissue was implanted into the rat subdermal space
for 14 and 60 days and the structural integrity and calcification were evaluated. As an in vivo valve replacement model, the
decellularized porcine valve was implanted in the pulmonary valve position in dogs and functional and histological evaluation
was performed after 1, 2, and 6 months. Histological examination showed that the newly developed detergent treatment effectively
removed cellular debris from the porcine aortic tissue. Decellularized porcine valve tissue implanted subdermally in rats
showed minimal inflammatory cell infiltration and calcification. In the valve replacement model, spontaneous reendothelialization
and repopulation of the medial cells were observed within 2 months, and good valve function without regurgitation was observed
by echocardiography up to 6 months. The minimally immunogenic decellularized porcine valve proved effective in mitigating
postimplant calcification and provided a suitable matrix for revitalizing prostheses through in situ recellularization, cellular
ingrowth, and tissue remodeling. 相似文献
32.
Masaki Iwai Yasutaka Ishu Yoshihiro Kitagawa Kazunobu Tada Motomu Kashiwadani Takeshi Okanoue Kei Kashima 《Medical molecular morphology》1993,26(3-4):207-210
The immunoreactivity of albumin (ALB) was observed in the hepatocytes of fetal rats on day 18 of gestation, and was especially observable in immature rough endoplasmic reticulum (rER) and Golgi apparatus (GA); by then, a small amount of silver grains of ALB mRNA could already be detected. Just after birth, immunoreactivity of ALB could be observed in fine granules or diffusely in all hepatocytes, and was present in rER and GA. One week after birth immunoreactivity of ALB was observed in all hepatocytes and was visible in developed rER and GA; the grains of ALB mRNA were present in all hepatocytes. 相似文献
33.
Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer 总被引:5,自引:0,他引:5
Ito R Oue N Yoshida K Kunimitsu K Nakayama H Nakachi K Yasui W 《Virchows Archiv : an international journal of pathology》2005,447(4):717-722
Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our
serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas.
CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric
carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics
and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal
metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression
was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive
CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases
that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression
of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis. 相似文献
34.
ABC proteins: key molecules for lipid homeostasis 总被引:2,自引:0,他引:2
Takahashi K Kimura Y Nagata K Yamamoto A Matsuo M Ueda K 《Medical molecular morphology》2005,38(1):2-12
Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein–cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures. 相似文献
35.
Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry 总被引:3,自引:0,他引:3
Yu P Constien R Dear N Katan M Hanke P Bunney TD Kunder S Quintanilla-Martinez L Huffstadt U Schröder A Jones NP Peters T Fuchs H de Angelis MH Nehls M Grosse J Wabnitz P Meyer TP Yasuda K Schiemann M Schneider-Fresenius C Jagla W Russ A Popp A Josephs M Marquardt A Laufs J Schmittwolf C Wagner H Pfeffer K Mudde GC 《Immunity》2005,22(4):451-465
The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype. 相似文献
36.
ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats 总被引:28,自引:1,他引:28
Nishitoh H Matsuzawa A Tobiume K Saegusa K Takeda K Inoue K Hori S Kakizuka A Ichijo H 《Genes & development》2002,16(11):1345-1355
Expansion of CAG trinucleotide repeats that encode polyglutamine is the underlying cause of at least nine inherited human neurodegenerative disorders, including Huntington's disease and spinocerebellar ataxias. PolyQ fragments accumulate as aggregates in the cytoplasm and/or in the nucleus, and induce neuronal cell death. However, the molecular mechanism of polyQ-induced cell death is controversial. Here, we show the following: (1) polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress-induced JNK activation and cell death. These findings suggest that ASK1 is a key element in ER stress-induced cell death that plays an important role in the neuropathological alterations in polyQ diseases. 相似文献
37.
Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury 总被引:5,自引:0,他引:5
Yamamoto K Tomita N Yoshimura S Nakagami H Taniyama Y Yamasaki K Ogihara T Morishita R 《International journal of molecular medicine》2004,14(4):633-640
Although injury of epithelial cells has been reported to be responsible for renal disease such as acute renal failure, its molecular mechanisms are largely unknown. As hypoxia has been postulated as the initial trigger of epithelial injury, we studied the molecular mechanisms of apoptosis induced by hypoxia in human renal epithelial cells. Severe hypoxia caused epithelial cell death, accompanied by a significant increase in LDH release (p<0.01). In addition, hypoxic treatment of epithelial cells resulted in a significant increase in apoptotic cells as assessed by cell morphology (p<0.01). The apoptotic change in epithelial cells under hypoxic condition was also confirmed by a significant increase in caspase-3-like activity and release of cytochrome c (p<0.01). The decrease in epithelial cell number was completely abolished by addition of a wide-spectrum caspase inhibitor, Z-VAD, rather than Z-DEVD, a specific caspase-3 inhibitor (p<0.01). Thus, we further studied the molecular mechanisms of apoptosis induced by hypoxia. Anti-apoptotic factors, Bcl-2 and Bcl-xL, were significantly decreased in epithelial cells under a hypoxic condition as assessed by Western blotting (p<0.01). In contrast, hypoxia did not alter their location. Of particular importance, translocation of a proapoptotic factor, Bax, from the cytoplasm to the mitochondrial membrane was observed in response to hypoxia, whereas total Bax protein was not changed by hypoxia. Overall, this study demonstrated that hypoxia caused epithelial cell death induced by caspase-3-like activity-dependent apoptosis. The pro-apoptotic mechanisms of hypoxia in epithelial cells largely depend on a significant decrease in Bcl-2 and Bcl-xL. In addition, the present results demonstrate that translocation of Bax from the cytosol to the mitochondrial membrane occurred under hypoxia, thereby leading to pathological tissue destruction. 相似文献
38.
The stereoregularity of poly(methyl vinyl ketone) (PMVK) was determined by NMR spectra of the polymers. Isotactic and atactic PMVK's were thermally degraded, and thermogravimetric analysis, IR and visible and UV spectroscopy were applied to elucidate the mechanism of the degradation. It was found that the isotactic polymer begins to degrade at lower temperature than the atactic polymer, but its rate becomes lower than that of the atactic polymer at temperatures higher than 320°C. If the two types of polymers were treated at a constant temperature (200°C) for varying times under N2 atmosphere, the isotactic polymer showed a higher degradation rate as determined by thermogravimetric analysis and IR spectroscopy. The isotactic polymer shows a higher tendency to form a monocyclic structure in the heat treatment than the atactic polymer. This is similar to poly(isopropenyl methyl ketone). 相似文献
39.
Toshiyuki Uryu Kenichi Hatanaka Kei Matsuzaki 《Macromolecular chemistry and physics.》1980,181(10):2137-2149
The cationic, ring-opening copolymerization of 1,6-anhydro-2,3,4-tri-O-benzyl-ß-D -glucopyranose with epichlorohydrin, 3,3-bis(chloromethyl)oxetane and 1,3-dioxolane was investigated with phosphorus pentafluoride as catalyst at low temperatures. Besides, copolymerization of 1,6-anhydro-2,3,4-tri-O-methyl-ß-D -glucopyranose with epichlorohydrin was studied. Structure and composition of the copolymers were determined by 1H and 13C NMR spectroscopy, indicating that copolymerization occurred in each combination of monomers. Number-average molecular weights of copolymers were in the range of 1 400 to 22 800. From the specific rotation and 13C NMR spectrum of copolymers, it was revealed that the ring-opening copolymerization of the benzylated 1,6-anhydro-glucopyranose with the cyclic monomers occurred in a stereoregular manner to give the C-1 carbon of glucose unit with α-configuration. Debenzylation of a copolymer prepared from 1,6-anhydro-2,3,4-tri-Obenzyl-ß-D -glucopyranose and 1,3-dioxolane gave a copolymer composed of free sugar units in the polymer main chain. Assignment of 13C NMR spectra of 2,3,4-tri-O-benzyl-ß-D -glucopyranan and of a copolymer of 1,6-anhydro-2,3,4-tri-O-benzyl-ß-ß-glucopyranose with 1,3-dioxolane was attempted. 相似文献
40.
Takaaki Hayashi Katsuhiro Hosono Akiko Kubo Kentaro Kurata Satoshi Katagiri Kei Mizobuchi Minehiro Kurai Norihito Mamiya Mineo Kondo Toshiaki Tachibana Hirotomo Saitsu Tsutomu Ogata Tadashi Nakano Yoshihiro Hotta 《American journal of medical genetics. Part A》2020,182(6):1500-1505
Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties. 相似文献