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31.
Kimberley A. Pitman Raphael Ricci Robert Gasperini Shannon Beasley Macarena Pavez Jac Charlesworth Lisa Foa Kaylene M. Young 《Glia》2020,68(2):376-392
Throughout life, oligodendrocyte progenitor cells (OPCs) proliferate and differentiate into myelinating oligodendrocytes. OPCs express cell surface receptors and channels that allow them to detect and respond to neuronal activity, including voltage-gated calcium channel (VGCC)s. The major L-type VGCC expressed by developmental OPCs, CaV1.2, regulates their differentiation. However, it is unclear whether CaV1.2 similarly influences OPC behavior in the healthy adult central nervous system (CNS). To examine the role of CaV1.2 in adulthood, we conditionally deleted this channel from OPCs by administering tamoxifen to P60 Cacna1c fl/fl (control) and Pdgfrα-CreER:: Cacna1c fl/fl (CaV1.2-deleted) mice. Whole cell patch clamp analysis revealed that CaV1.2 deletion reduced L-type voltage-gated calcium entry into adult OPCs by ~60%, confirming that it remains the major L-type VGCC expressed by OPCs in adulthood. The conditional deletion of CaV1.2 from adult OPCs significantly increased their proliferation but did not affect the number of new oligodendrocytes produced or influence the length or number of internodes they elaborated. Unexpectedly, CaV1.2 deletion resulted in the dramatic loss of OPCs from the corpus callosum, such that 7 days after tamoxifen administration CaV1.2-deleted mice had an OPC density ~42% that of control mice. OPC density recovered within 2 weeks of CaV1.2 deletion, as the lost OPCs were replaced by surviving CaV1.2-deleted OPCs. As OPC density was not affected in the motor cortex or spinal cord, we conclude that calcium entry through CaV1.2 is a critical survival signal for a subpopulation of callosal OPCs but not for all OPCs in the mature CNS. 相似文献
32.
Villagrán-García Macarena Muñiz-Castrillo Sergio Ciano-Petersen Nicolás Lundahl Vogrig Alberto Farina Antonio Villard Marine Psimaras Dimitri Alentorn Agusti Gonçalves David Fabien Nicole Rogemond Véronique Joubert Bastien Honnorat Jérôme 《Journal of neurology》2023,270(1):283-299
Journal of Neurology - The link between paraneoplastic neurological syndromes (PNS) and renal cell and bladder cancer (RCC/BC) is rare and uncertain. Our aim was to clinically evaluate, in light of... 相似文献
33.
Melanoma risk alleles are associated with downregulation of the MTAP gene and hypermethylation of a CpG island upstream of the gene in dermal fibroblasts 下载免费PDF全文
Antonella Sangalli Giovanni Malerba Gianpaolo Tessari Monica Rodolfo Macarena Gomez‐Lira 《Experimental dermatology》2017,26(8):733-736
Several association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition has not been elucidated. MTAP has a tumor suppressor activity and epigenetic silencing has been described in melanoma cell lines. In the present study, we show that melanoma risk alleles correlate with a MTAP allele‐specific hyper‐methylation and down‐regulation of gene expression. 相似文献
34.
Hyponatremic and hepatic encephalopathy are common causes of metabolic encephalopathy that may coexist in patients with cirrhosis.
The clinical picture is common to any metabolic encephalopathy and is characterized by a confusional syndrome that may evolve
into coma. Chronic mild or minimal manifestations can be seen in both, but motor symptoms are more common in hepatic encephalopathy.
Recent advances show that in addition to clinical manifestations both encephalopathies share some pathogenetic mechanisms.
Dysfunction of astrocytes, osmotic changes in the brain and brain edema are present in both situations. Recognition of these
abnormalities is important to plan therapy. New drugs that affect brain hydration may be useful for both encephalopathies. 相似文献
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36.
Banegas JR Rodríguez Artalejo F del Rey Calero J 《Revista espa?ola de salud pública》2000,74(4):327-339
In this article we are discussing a few of the contributions by the Austro-British philosopher Karl R. Popper, one of our most influential contemporary thinkers, whose epistemological and socio-political theories have also penetrated the sphere of epidemiology. We are focusing mainly on the so-called problem of induction. We sustain, in line with Popper, that the scientific method does not use inductive reasoning, but rather hypothetical-deductive reasoning. Although the movement from the data evaluating a hypothesis to a conclusion on the latter goes from the specific to the general, that is, in an inductive direction, the induction does not exist as a reasoning process or inference. That is, there is no method that enables us to infer or to verify hypotheses or theories (we cannot explore all of the possible situations to see whether the theory stands up), or even to render them very probable. Besides, scientists look for highly informative theories, not highly probable ones. What we actually do is to propose a hypothesis as a tentative solution to a problem, to confront the prediction deduced from the hypothesis with actual experience, and evaluate whether the hypothesis is rejected or not by the facts. As theories cannot be verified, we can only accept them if they withstand an attempt to reject them. Consequently, the test of a theory consists of criticism or a serious attempt at falsification, that is, the elimination of error within a theory, in order to reject it if it is false. The objective is, thus, the search for true theories. For this purpose, the scientific method uses a systematic set of methodological (not logical) rules, that is, decisions. These methodological rules or principles can be summed up in two: [symbol: see text]be inventive and critical!, that is, propose bold hypotheses and subject them to severe tests of experience. Logic plays its role mainly by allowing us to deduce from a hypothesis the predictions to be confronted with the facts or evidence. This is applicable both to statistical inference as well as to causal inference. We argue that the criteria of causality used in epidemiology are none other than rules of the method designed for the same purpose: they are concerned with eliminating or reducing errors (chance, bias...) on testing a causal hypothesis. Consequently, the so-called ausal inference, the step from evidence to causal theory, is not a logical inductive or probabilistic process but rather a decision based on the evaluation of a causal hypothesis thanks to methodological rules such as the criteria of causality. We believe that the interest of the debate between the Popperian and the inductivist epidemiologists is not merely a matter of words, as, if we are aware that we do not operate inductively, that we cannot establish firmly hypotheses, not even affirm them probabilistically, we will presumably adopt a humbler attitude and look more for the errors in our theories than for their facile examples of confirmation. 相似文献
37.
38.
T M Calero Moreno G Gustafsson S Garwicz D Grandér G K Jonmundsson B-M Frost A M?kipernaa O Rasool E-R Savolainen K Schmiegelow S S?derh?ll K Vettenranta F Wesenberg S Einhorn M Heyman 《Leukemia》2002,16(10):2037-2045
Inactivation of the Ink4 gene locus locus on 9p comprising the tumour suppressor gene p16ink4a and its neighbours p14ARF and p15ink4b is common in childhood acute lymphoblastic leukaemia (ALL), but the prognostic significance is controversial. DNA from 230 patients was retrospectively analysed by Southern blotting, single strand conformation polymorphism (SSCP) and sequencing techniques. The results were correlated with clinical characteristics and outcome. One hundred and ninety-four fully analysed patients, similarly treated using the Nordic NOPHO-86 or the current NOPHO-92 protocols, were included in the outcome analysis. Deletions approached a minimally deleted region between the p16ink4a and p15ink4b genes, making the p14ARF gene the most commonly deleted coding sequence. Bi-allelic deletion was associated with high white blood cell count (WBC) (P < 0.001), T cell phenotype (P < 0.001) and mediastinal mass (P < 0.001). Patients with Ink4 locus bi-allelic deletions had an inferior pEFS (P < 0.01) and multivariate analysis indicated that bi-allelic deletion of the p16ink4a and the p14ARF genes was an independent prognostic risk factor (P < 0.05). Sub-group analysis revealed a pronounced impact of deletion status for high-risk patients, ie with high WBC. Deletion-status and clinical risk criteria (WBC) could thus be combined to further differentiate risk within the high-risk group. The analysis of the Ink4 locus adds independent prognostic information in childhood ALL treated by Nordic protocols and may help in selection of patients for alternative treatment. 相似文献
39.
Jesús Joaquín Hijona Elósegui Miguel Calero RojasAna Contreras Rodríguez M. del Carmen Toledano MonteroCarmen Pallarés Ayuso Juan Manuel Torres Martí 《Progresos de Obstetricia y Ginecología》2008
Cervical pregnancy is a rare form of ectopic pregnancy with a high risk of hemorrhage. Early diagnosis is an important prognostic factor for survival and preserved fertility in these patients. We present the case of a patient diagnosed with cervical ectopic pregnancy in her seventh week of gestation. The therapeutic management was conservative and involved the combination of systemic and intra-amniotic methotrexate Because of the lower associated morbidity and mortality and the possibility of maintaining the patient’s fertility, conservative treatment is a viable therapeutic approach in cases such as that presented herein. 相似文献
40.
Rodríguez Corchero J Martín Calero J Martínez Rodríguez J Huesa Martínez I García Matilla F 《Actas urologicas espa?olas》2004,28(9):672-676
Renal artery aneurysm are uncommon. The true prevalence of renal aneurysms in the general population is unknown (less than 0.4%). Because of more widespread use of Angiography and CT as well as improved imaging techniques, they are diagnosed more frecuently. Fibromuscular dysplasia and arteriosclerotic occlusion of the renal artery are believed to be the most frecuent causes. In general, there are no pathognomonic signs and symptoms of renal aneurysm. Nonspecific complaints include flank pain, hematuria, hypertension and hypotension (suspect rupture of aneurysm). We report a case of a woman with a renal artery calcified aneurysm in a solitary kidney. 相似文献