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61.
Kennedy J Jackson GC Barker FS Nundlall S Bella J Wright MJ Mortier GR Neas K Thompson E Elles R Briggs MD 《Human mutation》2005,25(6):593-594
Pseudoachondroplasia (PSACH) and some forms of multiple epiphyseal dysplasia (MED) result from mutations in the gene encoding cartilage oligomeric matrix protein (COMP). COMP is a large pentameric glycoprotein found predominantly in the extracellular matrix of cartilage, tendon, and ligament. As a modular protein, it is composed of a coiled-coil domain, four type II (T2) repeats, eight type III (T3) repeats, and a large globular C-terminal domain (CTD). The majority (>85%) of COMP mutations causing PSACH or MED are found in the exons encoding the T3 repeats, and the disease mechanism has been characterised in detail. Much less is known about disease-causing mutations in the CTD; in 10 years only seven mutations have been identified. In this study, we describe eight novel and two recurrent mutations that we have recently identified in patients with PSACH or MED. Interestingly, these mutations result in a spectrum of disease, ranging from mild MED to severe PSACH. Mapping of all known COMP CTD mutations on a three-dimensional model of the C-terminal domain shows that the CTD mutations cluster in two distinct regions. These regions are probably important in stabilising the T3-CTD structure and mediating intra- or intermolecular interactions. 相似文献
62.
Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages 总被引:10,自引:0,他引:10
Raes G De Baetselier P Noël W Beschin A Brombacher F Hassanzadeh Gh G 《Journal of leukocyte biology》2002,71(4):597-602
Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi. 相似文献
63.
64.
Steve Stegen Claire-Sophie Devignes Sophie Torrekens Riet Van Looveren Peter Carmeliet Geert Carmeliet 《Journal of bone and mineral research》2021,36(3):604-616
Skeletal homeostasis critically depends on the proper anabolic functioning of osteolineage cells. Proliferation and matrix synthesis are highly demanding in terms of biosynthesis and bioenergetics, but the nutritional requirements that support these processes in bone-forming cells are not fully understood. Here, we show that glutamine metabolism is a major determinant of osteoprogenitor function during bone mass accrual. Genetic inactivation of the rate-limiting enzyme glutaminase 1 (GLS1) results in decreased postnatal bone mass, caused by impaired biosynthesis and cell survival. Mechanistically, we uncovered that GLS1-mediated glutamine catabolism supports nucleotide and amino acid synthesis, required for proliferation and matrix production. In addition, glutamine-derived glutathione prevents accumulation of reactive oxygen species and thereby safeguards cell viability. The pro-anabolic role of glutamine metabolism was further underscored in a model of parathyroid hormone (PTH)-induced bone formation. PTH administration increases glutamine uptake and catabolism, and GLS1 deletion fully blunts the PTH-induced osteoanabolic response. Taken together, our findings indicate that glutamine metabolism in osteoprogenitors is indispensable for bone formation. © 2020 American Society for Bone and Mineral Research (ASBMR). 相似文献
65.
The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death. 总被引:1,自引:0,他引:1
Irene Delgado Elena Domínguez-Frutos Thomas Schimmang Maria A Ros 《Developmental dynamics》2008,237(3):649-658
Here we analyze limb development after the conditional inactivation of Fgf8 from the epiblast, using the previously described MORE (Mox2Cre) line. This line drives variable mosaic recombination of a floxed Fgf8 allele, resulting in a small proportion of AER cells that maintain Fgf8 expression. The phenotype of Mox2Cre;Fgf8 limbs is most similar to that of Msx2Cre;Fgf8 forelimbs, indicating that a small but durable expression of FGF8 is equivalent to an early normal, but transitory, expression. This functional equivalence likely relies on the subsequent Fgf4 upregulation that buffers the differences in the pattern of Fgf8 expression between the two conditional mutants. The molecular analysis of Mox2Cre;Fgf8 limbs shows that, despite Fgf4 upregulation, they develop under reduced FGF signaling. These limbs also exhibit an abnormal area of cell death at the anterior forelimb autopod, overlapping with an ectopic domain of Bmp7 expression, which can explain the abnormal morphogenesis of the anterior autopod. 相似文献
66.
67.
Pousa BR da Silva Domínguez L Mora Bermúdez MJ Insua AM Santana Penín U 《Bulletin du Groupèment international pour la recherche scientifique en stomatologie & odontologie》1999,41(2-3):73-77
The length of the silent period (SP) has been subject of extensive researches and its use has been established for the diagnosis of dysfunctional individuals. Because of its great variability we should be cautious about its assessment. This study is aimed to find the normal values taken in symptomless subjects using a commercial/medical recording system, designed for clinical use. Thirty-six readings of the SP have been taken causing a chin tap. The assessment of the motor dysfunction and the subsequent depressed activity gave the result of 32.37 ms (SD = 19.47, ranged from 15 to 110). This is slightly more extended than the results described by the majority of the Authors. 相似文献
68.
To investigate the involvement of NADPH-diaphorase (NADPH-d)-containing neurons in Alzheimer's disease (AD), NADPH-d enzyme histochemistry in vibratome sections was applied to the superior frontal and superior temporal cortex and the neostriatum in 5 AD and 6 aged control brains. Overall there was a neuronal loss and atrophy in the cortex of AD. Despite slight morphological neuronal changes in the cortex of AD, we found no significant difference in the number of NADPH-d-positive neurons in both cortex and neostriatum between control and AD cases. These results provide further evidence for a selective preservation of NADPH-d neurons in AD. In order to check whether nNOS-immunoreactive neurons are identical to NADPH-d-positive neurons in the human brain, we examined the frontal and temporal cortex and neostriatum of normal human brains in serial cryostat sections. We found that nNOS-containing neurons paralleled NADPH-d-positive neurons in these brain regions. Copyrightz1999S.KargerAG,Basel 相似文献
69.
Domínguez J Lobato RD Madero S Benito-León J Rivas JJ Gómez PA 《Acta neurochirurgica》1999,141(3):269-272
Summary Idiopathic trigeminal neuropathy is a benign disorder where the main clinical feature is facial numbness limited to the territory
of one or more divisions of the trigeminal nerve, persisting for a few weeks to several years and in which no underlying disease
can be identified. The case of a 37-year-old man with a brief history of sensory and motor trigeminal symptoms who showed
magnetic resonance imaging (MRI) findings consistent with a small trigeminal neurinoma is reported. The patient was operated
on but no tumour could be found during surgery and a biopsy was taken from the portio major. Pathological diagnosis was chronic
non granulomatous inflammatory reaction with areas of coagulation necrosis. Control MRI showed complete resolution of the
trigeminal abnormalities. It is concluded that in patients with MRI findings suggestive of a small trigeminal schwannoma,
benign idiopathic trigeminal neuropathy should also be considered in the differential diagnosis. A conservative approach with
sequential MRI studies may avoid an unnecessary surgical exploration. 相似文献
70.
Domínguez-Cunchillos F Armendáriz P Pérez-Cabañas I Artieda C Oteiza F Sanz MA 《The British journal of surgery》1999,86(11):1470-1471