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181.
AM Waryah A Rehman ZM Ahmed Z-H Bashir SY Khan AU Zafar S Riazuddin TB Friedman S Riazuddin 《Clinical genetics》2009,76(3):270-275
Autosomal recessive nonsyndromic hearing impairment (ARNSHI) segregating in three unrelated, large consanguineous Pakistani families (PKDF528, PKDF859 and PKDF326) is linked to markers on chromosome 12q14.2-q15. This novel locus is designated DFNB74 . Maximum two-point limit of detection (LOD) scores of 5.6, 5.7 and 2.6 were estimated for markers D 12 S 313, D 12 S 83 and D 12 S 75 at θ = 0 for recessive deafness segregating in these three families. Haplotype analyses identified a critical linkage interval of 5.35 cM (5.36 Mb) defined by D 12 S 329 at 74.58 cM and D 12 S 313 at 79.93 cM. DFNB74 is the second ARNSHI locus mapped to chromosome 12, but the physical intervals do not overlap with one another. A locus contributing to the early onset, rapidly progressing hearing loss of A/J mice ( ahl4 , age-related hearing loss 4) was reported to map to chromosome 10 in a region of conserved synteny to DFNB74 , suggesting that ahl4 and DFNB74 may be due to mutations of the same gene in these two species. 相似文献
182.
Functional magnetic resonance (MR) encompasses a spectrum of techniques that depict physiological and molecular processes
before morphological changes are visible on conventional imaging. As understanding of the pathophysiological and biomolecular
processes involved in breast malignancies evolves, newer functional MR techniques can be employed that define early predictive
and surrogate biomarkers for monitoring response to chemotherapy. Neoadjuvant chemotherapy is increasingly used in women with
primary breast malignancies to down-stage the tumour and enable successful breast conservation surgery. It also plays a role
in the treatment of undetected micrometastases. Cardinal physiological features of tumours that occur as a result of interactions
between cancer cells, stromal cells and secreted factors and cytokines and how they change with treatment provide the opportunity
to detect changes in the tumour microenvironment prior to any morphological change. Through sequential imaging, tumour response
can be assessed and non-responders can be identified early to enable alternative therapies to be considered. This review summarises
the functional magnetic resonance biomarkers of response in patients with breast cancer that are currently available and under
development. We describe the current state of each biomarker and explore their potential clinical uses and limitations in
assessing treatment response. With the aid of selected interesting cases, biomarkers related to dynamic contrast-enhanced
MRI, diffusion-weighted MRI, T2*/BOLD and MR spectroscopy are described and illustrated. The potential of newer approaches,
such as MR elastography, are also reviewed. 相似文献
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184.
Background and purpose:
Thromboxane A2 and endothelial dysfunction are implicated in the development of pulmonary hypertension. The receptor-transduction pathway for U46619 (9,11-dideoxy-9α, 11α-methanoepoxy prostaglandin F2α)-induced contraction was examined in endothelium-intact (E+) and denuded (E−) rat pulmonary artery rings.Experimental approach:
Artery rings were mounted on a wire myograph under a tension of 7–7.5 mN at 37°C and gassed with 95% O2/5% CO2. Isometric recording was made by using Powerlab data collection and Chart 5 software.Key results:
Both E+ and E− contractile responses were sensitive to Rho-kinase inhibition and the chloride channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)benzoic acid]. The E+ response was sensitive to the store-operated calcium channel blockers SKF-96365 {1-[B-[3-(4-methoxyphenyl)propoxy]-4-methoxy-phenethyl]-1H-imidazole hydrochloride} and 2-APB (2-amino ethoxy diphenylborate) (75–100 µmol·L−1). The E− response was sensitive to 2-APB (10–30 µmol·L−1), a putative IP3 receptor antagonist, and the calcium and chloride channel blockers nifedipine, DIDS (4,4′-diisothiocyanostilbene-2,2′-disulphonic acid) and niflumic acid but was insensitive to SKF-96365. Inhibiting KV with 4-AP in E+ rings exposed a contraction sensitive to nifedipine, DIDS and niflumic acid, whereas inhibiting BKCa exposed a contraction sensitive to mibefradil, DIDS and niflumic acid. This indicates that removal of the endothelium allows the TP receptor to inhibit KV, which may involve coupling to phospholipase C, because inhibition of phospholipase C with (1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-y]amino]hexyl]– 1H-pyrrole-2,5-dione) switched the E− pathway to the E+ pathway. U73122Conclusions and implications:
The results from this study indicate that distinct transduction pathways can be employed by the TP receptor to produce contraction and that the endothelium is able to influence the coupling of the TP receptor.British Journal of Pharmacology (2009) 157, 581–596; doi:10.1111/j.1476-5381.2008.00084.x; published online 22 April 2009This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 相似文献185.
AM Holmes JA Rudd FD Tattersall Q Aziz PLR Andrews 《British journal of pharmacology》2009,157(6):865-880
Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms. 相似文献
186.
Marie-Jeanne Aarts Ien AM van de Goor Hans AM van Oers Albertine J Schuit 《BMC public health》2009,9(1):396
Background
Physical inactivity in children is a major health problem in The Netherlands as well as in many other Western countries. In addition to health promotion among parents and children, creating "active" neighbourhoods can contribute to the solution of this health problem. However, changing environmental characteristics is often the responsibility of policy sectors outside the Public Health domain. Therefore this project identifies and evaluates the possibilities of multi-sector policy measures to stimulate physical activity in children. 相似文献187.
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Summary 137 samples of intracranial tumours have been studied in proton NMR spectroscopy. T1 and T2 relaxation times are above those of normal grey and white matter. Differential diagnosis between benign and malignant brain tumours does not seem feasible upon proton T1 and T2 alone. Histological correlations allowed us to specify secondary changes accounting for T1 and T2 variations (oedema, microcyst, stroma reaction, necrosis). 相似文献