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71.
Ferrari S Kitson C Farley R Steel R Marriott C Parkins DA Scarpa M Wainwright B Evans MJ Colledge WH Geddes DM Alton EW 《Gene therapy》2001,8(18):1380-1386
Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal. 相似文献
72.
73.
Casiglia E Mazza A Tikhonoff V Basso G Martini B Scarpa R Pessina AC 《Advances in therapy》2004,21(6):357-369
Manidipine and lercanidipine are considered effective and safe in the treatment of chronic arterial hypertension and are equipotent
in reducing blood pressure (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo runin period, these
2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential
hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of the active treatment period, BP was significantly
reduced in comparison with the end of the placebo phase in both the manidipine and the lercanidipine groups, without significant
differences between the 2 drugs. Daytime BP was significantly reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine,
while smaller reductions were seen at nighttime. The smoothness index was the same with both drugs. Unlike lercanidipine,
manidipine significantly reduced both basal (-30%) and minimal vascular resistance (-39%), qualifying it as a potent vasodilator.
Despite vasodilation, heart rate was not increased but was even slightly reduced by treatment. Ankle-foot edema was observed
with both drugs but was less pronounced with manidipine, probably because of greater postcapillary dilatation. In conclusion,
manidipine and lercanidipine are both effective and safe in mild-to-moderate essential hypertension, although the former seems
to have a more favorable tolerability profile than the latter. 相似文献
74.
Fabio Scarpa Daria Sanna Tiziana Lai Piero Cossu Marco Curini-Galletti Marco Casu 《Conservation Genetics Resources》2016,8(4):411-413
The order Proseriata (Platyhelminthes) represents one of the most abundant soft-bodied meiofaunal groups. These minute interstitial organisms are characterized by a very simple morphology, which often hides the occurrence of cryptic species. Accordingly, molecular analyses are often needed to provide reliable taxonomic assessment and/or species identification. For these purposes the 18S and 28S rDNA genes have been so far the markers of choice. Here, we present a set of new primers for the sequencing of the whole ribosomal region in Proseriata, which improves the size of the sequenced segment from the current 3100 bp (18S + 28S D1–D6) to about 6300 bp. A broader molecular dataset may be used to achieve deeper insights on the systematics of Proseriata. 相似文献
75.
76.
Although neurodegenerative diseases are most prevalent in the elderly, in rare cases, they can also affect children. Lysosomal
storage diseases (LSDs) are a group of inherited metabolic neurodegenerative disorders due to deficiency of a specific protein
integral to lysosomal function, such as enzymes or lysosomal components, or to errors in enzyme trafficking/targeting and
defective function of nonenzymatic lysosomal proteins, all preventing the complete degradation and recycling of macromolecules.
This primary metabolic event determines a cascade of secondary events, inducing LSD’s pathology. The accumulation of intermediate
degradation affects the function of lysosomes and other cellular organelles. Accumulation begins in infancy and progressively
worsens, often affecting several organs, including the central nervous system (CNS). Affected neurons may die through apoptosis
or necrosis, although neuronal loss usually does not occur before advanced stages of the disease. CNS pathology causes mental
retardation, progressive neurodegeneration, and premature death. Many of these features are also found in adult neurodegenerative
disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. However, the nature of the secondary events and their
exact contribution to mental retardation and dementia remains largely unknown. Recently, lysosomal involvement in the pathogenesis
of these disorders has been described. Improved knowledge of secondary events may have impact on diagnosis, staging, and follow-up
of affected children. Importantly, new insights may provide indications about possible disease reversal upon treatment. A
discussion about the CNS pathophysiology involvement in LSDs is the aim of this review. The lysosomal involvement in adult
neurodegenerative diseases will also be briefly described. 相似文献
77.
Renzo Manara Angelica Rampazzo Mara Cananzi Leonardo Salviati Rodica Mardari Paola Drigo Rosella Tomanin Nicoletta Gasparotto Elena Priante Maurizio Scarpa 《Journal of inherited metabolic disease》2010,33(3):67-72
Mucopolysaccharidosis type II (MPS-II, Hunter disease) is a X-linked recessive disorder. Affected females are extremely rare, mostly due to skewed X chromosome inactivation. A few papers outline MPS-II brain magnetic resonance imaging (MRI) “gestalt” in males, but neuroradiological reports on females are still lacking. We present an 11-year-old girl affected by the severe form of MPS-II who was followed up over a time span of 8 years, focusing on clinical and brain MRI evolution. In the last 2.5 years, the patient has been treated with enzyme replacement therapy (ERT) with idursulfase (Elaprase?, Shire Human Genetic Therapies AB, Sweden). On brain and cervical MRI examination, abnormalities in our patient did not differ from those detected in male patients: J-shaped pituitary sella, enlargement of perivascular spaces, brain atrophy, mild T2-hyperintensity in the paratrigonal white matter, diffuse platyspondylia, and mild odontoid dysplasia with odontoid cup. Brain atrophy progressed despite ERT introduction, whereas perivascular space enlargement did not change significantly before and after ERT. Cognitive impairment worsened independently from the course of white matter abnormality. Despite a profound knowledge of genetic and biochemical aspects in MPS-II, neuroradiology is still poorly characterized, especially in female patients. Spinal and brain involvement and its natural course and evolution after ERT introduction still need to be clarified. 相似文献
78.
Stress urinary incontinence 3 years after pregnancy: correlation to mode of delivery and parity 总被引:1,自引:0,他引:1
Viviane Herrmann Katia Scarpa Paulo Cesar Rodrigues Palma Cassio Zanettini Riccetto 《International urogynecology journal》2009,20(3):281-288
The aim was to estimate the incidence of stress urinary incontinence 3 years after delivery and its correlation to mode of
delivery and parity. A longitudinal cohort study was conducted with 120 women at the Antenatal Clinic at the State University
of Campinas. There was a significant difference in the incidence of postpartum stress urinary incontinence (SUI) among patients
with SUI during pregnancy (p > 0.0001). Women that were asymptomatic during pregnancy and had vaginal delivery developed SUI 2.4 times more frequently
than after c-section (19.2% and 8.0%, respectively). The incidence of SUI after delivery dropped significantly in the primiparous
(p = 0.0073) and multiparous 2–3 (p < 0.0001), but not in the multiparous with four or more deliveries (66.7% to 60.0%) (p = 0.5637). A significant correlation has been observed between parity and SUI (p = 0.0299). Pregnancy possibly predisposes to SUI 3 years after delivery as well as parity. No significant correlation has
been demonstrated between mode of delivery and SUI. 相似文献
79.
80.
Asha Balakrishnan Junia Y. Penachioni Simona Lamba Fonnet E. Bleeker Carlo Zanon Monica Rodolfo Viviana Vallacchi Aldo Scarpa Lara Felicioni Matthias Buck Antonio Marchetti Paolo M. Comoglio Alberto Bardelli Luca Tamagnone 《Human mutation》2009,30(8):1167-1174
Plexins are transmembrane high‐affinity receptors for semaphorins, regulating cell guidance, motility, and invasion. Functional evidences implicate semaphorin signals in cancer progression and metastasis. Yet, it is largely unknown whether plexin genes are genetically altered in human tumors. We performed a comprehensive gene copy analysis and mutational profiling of all nine members of the plexin gene family (plexinome), in melanomas and pancreatic ductal adenocarcinomas (PDACs), which are characterized by high metastatic potential and poor prognosis. Gene copy analysis detected amplification of PLXNA4 in melanomas, whereas copy number losses of multiple plexin genes were seen in PDACs. Somatic mutations were detected in PLXNA4, PLXNB3, and PLXNC1; providing the first evidence that these plexins are mutated in human cancer. Functional assays in cellular models revealed that some of these missense mutations result in loss of plexin function. For instance, c.1613G>A, p.R538H mutation in the extracellular domain of PLXNB3 prevented binding of the ligand Sema5A. Moreover, although PLXNA4 signaling can inhibit tumor cell migration, the mutated c.5206C>T, p.H1736Y allele had lost this activity. Our study is the first systematic analysis of the “plexinome” in human tumors, and indicates that multiple mutated plexins may be involved in cancer progression. Hum Mutat 30,1–8, 2009. © 2009 Wiley‐Liss, Inc. 相似文献