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1.
M. Larsabal S. Ly E. Sbidian M. Moyal-Barracco J.-N. Dauendorffer N. Dupin M.A. Richard O. Chosidow M. Beylot-Barry 《The British journal of dermatology》2019,180(3):647-656
Psoriasis is a common chronic inflammatory skin disease, affecting about 3% of the general population and approximately 2.5 million people in France, where this study took place. The genital area may be affected, however prevalence is poorly understood, meaning we do not know exactly how commonly this occurs. While it affects quality of life, genital psoriasis is under-recognized, probably due to the reluctance of patients to discuss genital involvement and sexual quality of life. The aims of this study, called the GENIPSO study, were to determine the prevalence of genital psoriasis, its clinical characteristics (its symptoms), whether it is associated with a particular type of psoriasis, and its impact on quality of life. The study included 776 adults seeing their doctor for psoriasis between November 2016 and March 2017. Among them, 336 (43.2%) had genital psoriasis. All these patients were aware that they had psoriasis on their genitals (genital lesions) but only 135 (40%) had already had a genital medical examination. Genital lesions were associated with (linked to) male gender, more severe psoriasis, first developing psoriasis when aged over 20 years, psoriasis of the skin folds, psoriasis on the scalp, nail and external auditory (ear) canal, but they were not associated with obesity or psoriatic arthritis. Itching was the main symptom. Genital psoriasis was associated with reduced quality of life and sexual health. The study found that genital psoriasis has a high prevalence in patients seeing their doctors about their psoriasis generally, it affects quality of life and should be better taken into account by dermatologists for the best possible care for patients. 相似文献
2.
Se-Jin Lee Adam Lehar Yewei Liu Chi Hai Ly Quynh-Mai Pham Michael Michaud Renata Rydzik Daniel W. Youngstrom Michael M. Shen Vesa Kaartinen Emily L. Germain-Lee Thomas A. Rando 《Proceedings of the National Academy of Sciences of the United States of America》2020,117(49):30907
Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit skeletal muscle growth (for review, see ref. 1). Mice lacking MSTN exhibit dramatic increases in muscle mass throughout the body, with individual muscles growing to about twice the normal size (2). MSTN appears to play two distinct roles in regulating muscle size, one to regulate the number of muscle fibers that are formed during development and a second to regulate the growth of those fibers postnatally. The sequence of MSTN has been highly conserved through evolution, with the mature MSTN peptide being identical in species as divergent as humans and turkeys (3). The function of MSTN has also been conserved, and targeted or naturally occurring mutations in MSTN have been shown to cause increased muscling in numerous species, including cattle (3–5), sheep (6), dogs (7), rabbits (8), rats (9), swine (10), goats (11), and humans (12). Numerous pharmaceutical and biotechnology companies have developed biologic agents capable of blocking MSTN activity, and these have been tested in clinical trials for a wide range of indications, including Duchenne and facioscapulohumeral muscular dystrophy, inclusion body myositis, muscle atrophy following falls and hip fracture surgery, age-related sarcopenia, Charcot–Marie–Tooth disease, and cachexia due to chronic obstructive pulmonary disease, end-stage kidney disease, and cancer.The finding that certain inhibitors of MSTN signaling can increase muscle mass even in Mstn−/− mice revealed that the function of MSTN as a negative regulator of muscle mass is partially redundant with at least one other TGF-β family member (13, 14), and subsequent studies have identified activin A as one of these cooperating ligands (15, 16). MSTN and activin A share many key regulatory and signaling components. For example, the activities of both MSTN and activin A can be modulated extracellularly by naturally occurring inhibitory binding proteins, including follistatin (17, 18) and the follistatin-related protein, FSTL-3 or FLRG (19, 20). Moreover, MSTN and activin A also appear to share receptor components. Based on in vitro studies, MSTN is capable of binding initially to the activin type II receptors, ACVR2 and ACVR2B (also called ActRIIA and ActRIIB) (18) followed by engagement of the type I receptors, ALK4 and ALK5 (21). In previous studies, we presented genetic evidence supporting a role for both ACVR2 and ACVR2B in mediating MSTN signaling and regulating muscle mass in vivo. Specifically, we showed that mice expressing a truncated, dominant-negative form of ACVR2B in skeletal muscle (18) or carrying deletion mutations in Acvr2 and/or Acvr2b (13) have significantly increased muscle mass. One limitation of the latter study, however, was that we could not examine the consequence of complete loss of both receptors using the deletion alleles, as double homozygous mutants die early during embryogenesis (22). Moreover, the roles that the two type I receptors, ALK4 and ALK5, play in regulating MSTN and activin A signaling in muscle in vivo have not yet been documented using genetic approaches. Here, we present the results of studies in which we used floxed alleles for each of the type II and type I receptor genes in order to target these receptors alone and in combination in muscle fibers. We show that these receptors are functionally redundant and that signaling through each of these receptors contributes to the overall control of muscle mass. 相似文献
3.
Kathleen R. Delaney RN NP DNSc 《Journal of child and adolescent psychiatric nursing》2006,19(4):194-202
Milieu relationships provide the critical background presence to staff's attempts to motivate, regulate, and teach patients how to cope with stress. Forging a connection with hospitalized children and adolescents demands attention to how they respond to adults and engage with staff around milieu expectations. Assessment guides that deal with these issues are presented. Important aspects of children's relatedness are presented in the context of their working models of adults and the influence of these representations on their response to staff. Coping skills are explained with particular emphasis on behavioral coping strategies. Tied to the assessment process are interventions that emphasize staff's role in helping patients manage strong affects and avoid the use of nonproductive behavior regulation strategies. 相似文献
4.
5.
Long-term effects of physiologic concentrations of dexamethasone on human bone-derived cells 总被引:2,自引:0,他引:2
M M Wong L G Rao H Ly L Hamilton J Tong W Sturtridge R McBroom J E Aubin T M Murray 《Journal of bone and mineral research》1990,5(8):803-813
Bone cells derived from human trabecular explants display osteoblastic features. We examined the modulation of alkaline phosphatase activity and cAMP production as the result of exposing trabecular explants to physiologic concentrations of dexamethasone for 4 weeks during cellular outgrowth and subculture. Cells treated with dexamethasone were observed to grow generally more slowly than control cells. Cells appeared larger and more polygonal, and staining for alkaline phosphatase was more intense in the dexamethasone-exposed cultures. There was a progressive increase in cellular PTH responsiveness with increasing duration of exposure of cells to dexamethasone. Cells grown for 6 weeks in 3 x 10(-8) M dexamethasone had a 10-fold increase in PTH-stimulated cyclic AMP accumulation. Dexamethasone-treated cells also had a significantly increased alkaline phosphatase activity. 1,25-(OH)2D3-stimulated alkaline phosphatase activity was increased approximately 20-fold. cAMP responses were significantly increased to PTH (21.7-fold), PGE1 (2.67-fold), and forskolin (4.81-fold), but not to cholera toxin. Dexamethasone-treated cells also had a mean decrease in 1,25-(OH)2D3-stimulated osteocalcin production to 26.2% of control values (p less than 0.001). Hydrocortisone treatment gave rise to similar effects but of smaller magnitude than those of dexamethasone. Testosterone did not have a significant effect on alkaline phosphatase activity or cAMP production. Skin fibroblasts showed a significant enhancement of alkaline phosphatase activity in response to dexamethasone, but of a much smaller magnitude than in bone cells. The phenotypic changes induced by long-term culture in dexamethasone are consistent with the promotion of a more differentiated osteoblastic phenotype. 相似文献
6.
7.
8.
Anderson RA; Evans LW; Irvine DS; McIntyre MA; Groome NP; Riley SC 《Human reproduction (Oxford, England)》1998,13(12):3319-3325
Follistatin is a binding protein for the activin and inhibin family of
hormones, regulating their biological activity. In the male reproductive
tract, the interaction of these factors is likely to be involved in the
regulation of the proliferation of several cell types. We have investigated
the presence of follistatin and activin A in seminal plasma using specific
immunoassays and have localized follistatin and activin/inhibin subunits in
the adult human testis, prostate and seminal vesicle to establish their
likely sources. High concentrations of immunoreactive follistatin were
present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in
peripheral plasma) and were similar in men with oligo/azoospermia and
following vasectomy. Follistatin immunoreactivity was localized to both
Leydig and Sertoli cells of the testis, and to epithelial cells of the
prostate gland and seminal vesicle, which are likely to be the predominant
sources of the hormone in seminal plasma. Activin A was also present in
seminal plasma in normal men but was undetectable following vasectomy, thus
deriving from the testis. Consistent with this finding, the betaA-subunit
was immunolocalized in Sertoli and Leydig cells but was not present in
seminal vesicle or prostate gland. The functional significance of the high
concentrations of follistatin secreted into seminal plasma by the prostate
gland and/or seminal vesicle is uncertain, but they may regulate the
biological activity of testis-derived activin A and inhibin B.
相似文献
9.
10.
G.D Burchard Guissé-Sow Diop Ly Lanuit Gryseels & Gressner 《Tropical medicine & international health : TM & IH》1998,3(3):234-241
Summary Four hundred and seventy villagers of Ndombo, a village with recently established intensive transmission of Schistosoma mansoni in the Senegal River Basin, were enrolled in a study with the intention to assess hepatosplenic morbidity. All patients were examined parasitologically and by ultrasound. Hepatic fibrosis serum markers were determined in 153 adult patients (aminoterminal propeptide of procollagen type III, hyaluronan and laminin). By ultrasound, about 60% of the patients showed early stages of hepatic involvement, 3% of the patients unequivocally showed severe hepatosplenic pathology (grade 3 according to the Managil classification), whereas in another study performed in the same village 3 years earlier, no patients with severe hepatosplenic pathology had been found. No correlation between the aminoterminal propeptide of procollagen type III, hyaluronan or laminin and the ultrasound findings could be established. These hepatic fibrosis serum markers do not seem to be a sensitive method to detect early hepatic fibrosis in schistosomiasis. 相似文献