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991.
992.
Arredi B Ferlin A Speltra E Bedin C Zuccarello D Ganz F Marchina E Stuppia L Krausz C Foresta C 《Journal of medical genetics》2007,44(3):205-208
Background
A limited number of studies aimed at investigating the possible association of Y‐chromosome haplogroups with microdeletions of the azoospermia factors (AZFs) or with particular infertile phenotypes, but definitive conclusions have not been attained. The main confounding elements in these association studies are the small sample sizes and the lack of homogeneity in the geographical origin of studied populations, affecting, respectively, the statistical power and the haplogroup distribution.Materials and methods
To assess whether some Y‐chromosome haplogroups are predisposing to, or protecting against, azoospermia factor c (AZFc; b2/b4) deletions, 31 north Italian patients carrying the AZFc b2/b4 microdeletion were characterised for 8 Y‐chromosome haplogroups, and compared with the haplogroup frequency shown by a north Italian population without the microdeletion (n = 93).Results and discussion
A significant difference was observed between the two populations, patients with microdeletions showing a higher frequency of the E haplogroup (29.3% vs 9.7%, p<0.01). The geographical homogeneity of the microdeleted samples and of the control population, controlled at microgeographical level, allows the possibility that the geographical structure of the Y genetic variability has affected our results to be excluded.Conclusion
Thus, it is concluded that in the north Italian population Y‐chromosome background affects the occurrence of AZFc b2/b4 deletions.Y‐chromosome long‐arm microdeletions are found in 5–10% of men with severe oligospermia and non‐obstructive azoospermia, and encompass one or more azoospermia factor (AZF) loci. Deletions of the azoospermia factor c (AZFc) region are clearly among the most commonly known molecular causes of spermatogenic failure in men.1 These deletions are caused by homologous recombination between the 229‐kb‐long b2 and b4 amplicons2 and span 3.5 Mb. Eight different gene families are removed by AZFc deletions, including all members of the DAZ gene family, which represents the stronger candidate for the AZFc phenotype.1,2,3,4,5,6,7 Although all AZFc deletions are essentially identical in molecular extension, people carrying these microdeletions present variable infertile phenotypes, suggesting the involvement of environmental factors and/or other genetic regions. Furthermore, the function of the AZF genes in human spermatogenesis and the role of the Y‐chromosome background in the predisposition to occurrence of deletions is still largely unknown.At present, around 250 Y single‐nucleotide polymorphisms have been discovered and their phylogenetic relationships are well known.8 These polymorphic markers of the male‐specific region of the Y chromosome define monophyletic groups of the Y chromosome, which hereafter we will name as “haplogroups”.A limited number of studies have investigated the possible association of Y‐chromosome haplogroups with microdeletions or with a particular infertile phenotype,9 but the contribution of predisposing factors or genetic background to causing deletions is still debated. In particular, only three studies have investigated the possible association between Y‐chromosome haplogroups and AZF deletions,10,11,12 all of them failing to establish important associations. These works studied such associations in an European population involving 73 microdeleted samples of heterogeneous geographical origin,10 in a northwestern European population involving 50 patients11 and in a Japanese population, more geographically localised but represented by a very low number of people with microdeletions (six patients).12 All the previous studies that found some suggestion of an association with Y‐chromosome haplogroups dealt with infertility. They reported a considerable over‐representation of the haplogroup K(xL,N,O1,O3c,P) in Danish men with reduced sperm count, which did not reach significance probably because of a small sample size,13 and D2b Y lineage in Japanese men with reduced sperm count,14 not confirmed by a later study.12However, these association studies require particular attention to two principal factors: (1) the geographical structure of the Y‐chromosome variations in the population under investigation, because the Y‐chromosome genetic variability is highly geographically structured and the Y‐haplogroup distribution changes over different geographical areas15; and (2) the number and selection criteria of the patient and control groups.To assess whether some Y‐chromosome haplogroups predispose to, or protect against, AZFc deletion, we have defined and compared Y‐chromosome haplogroup distribution in a group of unrelated Italian infertile men harbouring the b2/b4 deletion (n = 41, 31 of whom were from north Italy) and in a control group represented by fertile men without microdeletions (fathers of at least one child) from north Italy (n = 93). 相似文献993.
Rossi D De Smet P Lyfenko A Galli L Lorenzini S Franci D Petrioli F Orrico A Angelini C Tegazzin V Dirksen R Sorrentino V 《Journal of medical genetics》2007,44(2):e67
A novel single-nucleotide deletion in exon 100 of the RYR1 gene, corresponding to deletion of nucleotide 14,510 in the human RyR1 mRNA (c14510delA), was identified in a man with malignant hyperthermia and in his two daughters who were normal for malignant hyperthermia. This deletion results in a RyR1 protein lacking the last 202 amino acid residues. All three subjects heterozygotic for the mutated allele presented with a prevalence of type 1 fibres with central cores, although none experienced clinical signs of myopathy. Expression of the truncated protein resulted in non-functional RYR1 calcium release channels. Expression of wild-type and RyR1(R4836fsX4838) proteins resulted in heterozygotic release channels with overall functional properties similar to those of wild-type RyR1 channels. Nevertheless, small differences in sensitivity to calcium and caffeine were observed in heterotetrameric channels, which also presented an altered assembly/stability in sucrose-gradient centrifugation analysis. Altogether, these data suggest that altered RYR1 tetramer assembly/stability coupled with subtle chronic changes in Ca2+ homoeostasis over the long term may contribute to the development of core lesions and incomplete malignant hyperthermia susceptibility penetrance in individuals carrying this novel RYR1 mutation. 相似文献
994.
995.
996.
Sireci G Russo D Dieli F Porcelli SA Taniguchi M La Manna MP Di Liberto D Scarpa F Salerno A 《European journal of immunology》2007,37(2):425-433
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells. 相似文献
997.
Marcacci M Nofrini L Iacono F Di Martino A Bignozzi S Lo Presti M 《Computers in biology and medicine》2007,37(12):1771-1779
Revision total knee arthroplasty (RTKA) is a skill-demanding intervention presenting several technical challenges to the surgeon due to bone deficiencies and lack of anatomical references. Computer-assisted navigation systems can potentially solve these problems. An innovative computer-assisted surgical technique for RTKA is presented. The system is image free. Based on anatomical landmarks acquired on the patient, the system automatically plans the intervention, and provides the surgeon with tools to analyse and modify the proposed plan and to accurately reproduce it on the patient. Although we performed few cases with this navigated procedure, early results obtained demonstrated to be very promising. 相似文献
998.
Sebastiano Mercadante Francesco Masedu Marco Maltoni Daniela De Giovanni Luigi Montanari Cristina Pittureri 《Current medical research and opinion》2018,34(7):1187-1192
Aim: To assess the prevalence and intensity of constipation in advanced-cancer patients referred to palliative care, and to assess changes after 1 week of specialist palliative care.Methods: This was a prospective multi-center study in advanced patients for a period of 1 year. At admission (T0), age, gender, primary tumor, concomitant diseases, Karnofsky status, Palliative prognostic score (PaP), Edmonton Symptom Assessment scale (ESAS), Memorial Delirium Assessment Scale (MDAS), and bowel function index (BFI) were collected. In BFI, high values represent severe constipation. The use of medication was also recorded, as well as possible causes of constipation. The same parameters were recorded 1 week after admission for palliative care (T7).Results: A total of 246 patients were screened for constipation. The mean BFI at T0 was 42.4 (SD?=?26.92). One hundred and sixty-three patients (66.3%) had a BFI >28. The mean BFI at T7 was 35.7 (SD?=?28.8), with a significant decrease from T0 to T7 (p?=?.000). A significant decrease of BFI in patients with a BFI >28 was reported (p?=?.000). In patients with a BFI ≤28 there was a significant worsening of constipation (p?=?.000). In patients with a BFI >28 at T0 there was a significant increase in the use of laxatives at T7 in comparison with patients having a BFI ≤28 (p?=?.002). In patients with a BFI ≤28 at T0, who had a significant worsening of BFI (Δ?>?12), the use of laxatives was significantly lower in comparison to patients who had a BFI >28 (p?=?.000). In the multivariate analysis, dehydration and the use of benzodiazepines were independently associated with higher BFI scores.Conclusion: Constipation is present in approximately two-thirds of patients, and is principally associated with dehydration and the use of benzodiazepines. Patients with normal bowel function at initial assessment may see a worsening in their condition a week later due to lack of prevention or subsequent under-treatment. 相似文献
999.
Michele Bartoletti Sara Tedeschi Renato Pascale Luigi Raumer Alberto Enrico Maraolo Giulia Palmiero Fabio Tumietto Francesco Cristini Simone Ambretti Maddalena Giannella Russell Edward Lewis Pierluigi Viale 《International journal of antimicrobial agents》2018,51(3):516-521
Objectives
We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra–abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.Methods
We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves.Results
We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002–0.72, P?=?0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68–2.78, P?=?0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03–0.71, P?=?0.02), but not CRE (HR 1.12, 95% CI 0.45–2.83, P?=?0.80). All-cause 30-day mortality was similar in the two groups (P?=?0.46).Conclusion
TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation. 相似文献1000.
Laura?VerganiEmail author Giulia?Vecchione Francesca?Baldini Elena?Grasselli Adriana?Voci Piero?Portincasa Pier?Francesco?Ferrari Bahar?Aliakbarian Alessandro?A.?Casazza Patrizia?Perego 《European journal of nutrition》2018,57(5):1793-1805