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901.
Mechanotransduction of bone cells<Emphasis Type="Italic">in vitro</Emphasis>: Mechanobiology of bone tissue 总被引:11,自引:0,他引:11
Mullender M El Haj AJ Yang Y van Duin MA Burger EH Klein-Nulend J 《Medical & biological engineering & computing》2004,42(1):14-21
Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone
cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the
load profile and whether different components, such as fluid shear, tension or compression, can influence cells in differing
ways. During dynamic loading of intact bone, fluid is pressed through the osteocyte canaliculi, and it has been demonstrated
that fluid shear stress stimulates osteocytes to produce signalling molecules. It is less clear how mechanical loads act on
mature osteoblasts present on the surface of cancellous or trabecular bone. Although tissue strain and fluid shear stress
both cause cell deformation, these stimuli could excite different signalling pathways. This is confirmed by our experimental
findings, in human bone cells, that strain applied through the substrate and fluid flow stimulate the release of signalling
molecules to varying extents. Nitric oxide and prostaglandin E2 values increased by between two- and nine-fold after treatment with pulsating fluid flow (0.6±0.3 Pa). Cyclic strain (1000
μstrain) stimulated the release of nitric oxide two-fold, but had no effect on prostaglandin E2. Furthermore, substrate strains enhanced the bone matrix protein collagen I two-fold, whereas fluid shear caused a 50% reduction
in collagen I. The relevance of these variations is discussed in relation to bone growth and remodelling. In applications
such as tissue engineering, both stimuli offer possibilities for enhancing bone cell growth in vitro. 相似文献
902.
Litjens NH Rademaker M Ravensbergen B Rea D van der Plas MJ Thio B Walding A van Dissel JT Nibbering PH 《European journal of immunology》2004,34(2):565-575
Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-gamma. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells, this study focussed on effects of monomethylfumarate (MMF, bioactive metabolite of FAE) on polarization of monocyte-derived DC. MMF-incubated, lipo-polysaccharide-stimulated DC (MMF-DC) produced dramatically (p<0.05) reduced levels of IL-12p70 and IL-10 (8+/-4% and 20+/-4%, respectively) compared to control DC. MMF-DC were mature. MMF affected polarization of DC irrespective of polarization factor(s) and ligands for the various Toll-like receptors used. Coculture of MMF-DC with naive and primed allogenous Th cells resulted in lymphocytes producing less IFN-gamma, i.e. 59% and 54% of that by the respective Th cells cocultured with control DC. IL-4 production by primed, but not naive Th cells cocultured with MMF-DC was decreased as compared to cocultures with control DC. IL-10 production by naive and primed Th cells cocultured with MMF-DC and control DC did not differ. In addition, MMF inhibited LPS-induced NF-kappaB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-gamma production by Th cells. 相似文献
903.
Pattyn A Simplicio N van Doorninck JH Goridis C Guillemot F Brunet JF 《Nature neuroscience》2004,7(6):589-595
904.
Marjolein Wals Jim van Os Catrien G Reichart Manon H J Hillegers Johan Ormel Frank C Verhulst Willem A Nolen 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2004,(1):35-41
The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family. 相似文献
905.
Goddijn Mariette; Joosten Hannie; Knegt Lia; van der Veen Fulco; Franssen Maureen; Bonsel Gouke; Leschot Nico 《Human reproduction (Oxford, England)》2004,19(9):2172
Sir, We thank Mayumi Sugiura-Ogasawara et al. for their commentson our paper (Goddijn et al., 2004 相似文献
906.
Michael Bilous Mitch Dowsett Wedad Hanna Jorma Isola Annette Lebeau Aberlardo Moreno Frédérique Penault-Llorca Josef Rüschoff Gorana Tomasic Marc van de Vijver 《Modern pathology》2003,16(2):173-182
Knowledge of HER2 status is a prerequisite when considering a patient's eligibility for Herceptin (trastuzumab) therapy. Accurate assessment of HER2 status is essential to ensure that all patients who may benefit from Herceptin are correctly identified. There are several assays available to determine HER2 status: the most common in routine clinical practice are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Various factors can affect the results achieved with these assays, including the assay antibody/probe, the methodology and the experience of personnel. Many countries have implemented national testing guidelines in an attempt to standardize testing procedures and make results more accurate. These guidelines vary in the level of detail and the number of recommendations. This review looks at areas of consensus between the different national testing guidelines and highlights where errors may arise during the testing procedure. The key point underlined by this review is that whatever method is used to test for HER2 status, the technology must be validated first, and there must be regular internal and external quality control and quality assurance procedures. 相似文献
907.
Ossewaarde ME Bots ML van der Schouw YT de Kleijn MJ Wilmink HW Bak AA Planellas J Banga JD Grobbee DE 《Maturitas》2003,45(1):47-54
OBJECTIVES: To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. METHODS: Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. RESULTS: Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. CONCLUSIONS: The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids. 相似文献
908.
Chan YB Miguel-Aliaga I Franks C Thomas N Trülzsch B Sattelle DB Davies KE van den Heuvel M 《Human molecular genetics》2003,12(12):1367-1376
Autosomal recessive spinal muscular atrophy (SMA) is linked to mutations in the survival motor neuron (SMN) gene. The SMN protein has been implicated at several levels of mRNA biogenesis and is expressed ubiquitously. Studies in various model organisms have shown that the loss of function of the SMN gene leads to embryonic lethality. The human contains two genes encoding for SMN protein and in patients one of these is disrupted. It is thought the remaining low levels of protein produced by the second SMN gene do not suffice and result in the observed specific loss of lower motor neurons and muscle wasting. The early lethality in the animal mutants has made it difficult to understand why primarily these tissues are affected. We have isolated a Drosophila smn mutant. The fly alleles contain point mutations in smn similar to those found in SMA patients. We find that zygotic smn mutant animals show abnormal motor behavior and that smn gene activity is required in both neurons and muscle to alleviate this phenotype. Physiological experiments on the fly smn mutants show that excitatory post-synaptic currents are reduced while synaptic motor neuron boutons are disorganized, indicating defects at the neuromuscular junction. Clustering of a neurotransmitter receptor subunit in the muscle at the neuromuscular junction is severely reduced. This new Drosophila model for SMA thus proposes a functional role for SMN at the neuromuscular junction in the generation of neuromuscular defects. 相似文献
909.
Westerterp M Busch OR Bergman JJ Ten Kate FJ van Lanschot JJ 《Journal of clinical pathology》2005,58(12):1325-1327
This case report describes a 70 year old woman with excessive diffuse keratinisation of the oral cavity and oesophagus harbouring a squamous cell carcinoma. This excessive diffuse keratinisation of normally non-keratinised squamous epithelium could not be identified in normally non-keratinised epithelia in other parts of the body (the vagina), arguing against a genetic basis for this disorder. The term "crackleware" oesophagus was used to describe this entity, which has not been described previously in the English literature. 相似文献
910.
Valianpour F Selhorst JJ van Lint LE van Gennip AH Wanders RJ Kemp S 《Molecular genetics and metabolism》2003,79(3):189-196
Elevated levels of very long-chain fatty acids (VLCFA) in plasma and tissues are the biochemical hallmark for patients with X-linked adrenoleukodystrophy (X-ALD). Current methods for the determination of VLCFA levels are laborious and time-consuming. We describe a rapid and easy method using electrospray ionization mass spectrometry (ESI-MS) with deuterated internal standards. VLCFA are hydrolyzed, extracted, and quantified in less than 4h. This includes 2h of hydrolysis and 4min of quantification. We validated the method by analyzing 60 plasma samples from controls and patients with X-ALD or Zellweger syndrome using both the ESI-MS protocol and an established method for VLCFA analysis using gas chromatography (GC). The C26:0 concentrations determined with ESI-MS in plasma and fibroblasts of X-ALD patients are in good agreement with those reported previously for GC and GC-MS. Besides saturated straight chain VLCFA, we also determined the concentrations of the mono-unsaturated VLCFA C24:1 and C26:1 and established that while C24:1 levels are not elevated, C26:1 levels are elevated in both plasma and fibroblasts from X-ALD patients. 相似文献