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101.
Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders? 总被引:3,自引:2,他引:3
Based on cytogenetic observations, several syndromes have been previously
identified as microdeletion-based disorders. In this review, recent
progress is presented regarding whether one or multiple genes can be
implicated in the pathogenesis of these segmentally aneusomic syndromes.
The syndromes discussed include Angelman, Alagille, Williams,
Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and
DiGeorge/velocardiofacial or the 22q11 deletion syndromes. For Angelman and
Alagille syndromes, single genes have been identified, whereas for Williams
and Langer-Giedion syndromes, more than one gene can be implicated.
Although there has been significant progress in dissecting the molecular
basis for the other disorders, the ultimate answer regarding one versus
several genes remains to be determined.
相似文献
102.
Acute changes in short-term plasticity at synapses with elevated levels of neuronal calcium sensor-1 总被引:1,自引:0,他引:1
Short-term synaptic plasticity is a defining feature of neuronal activity, but the underlying molecular mechanisms are poorly understood. Depression of synaptic activity might be due to limited vesicle availability, whereas facilitation is thought to result from elevated calcium levels. However, it is unclear whether the strength and direction (facilitation versus depression) of plasticity at a given synapse result from preexisting synaptic strength or whether they are regulated by separate mechanisms. Here we show, in rat hippocampal cell cultures, that increases in the calcium binding protein neuronal calcium sensor-1 (NCS-1) can switch paired-pulse depression to facilitation without altering basal synaptic transmission or initial neurotransmitter release probability. Facilitation persisted during high-frequency trains of stimulation, indicating that NCS-1 can recruit 'dormant' vesicles. Our results suggest that NCS-1 acts as a calcium sensor for short-term plasticity by facilitating neurotransmitter output independent of initial release. We conclude that separate mechanisms are responsible for determining basal synaptic strength and short-term plasticity. 相似文献
103.
Diane J. Pincus MD Teresa R. Humeston BS Richard J. Martin MD 《The Journal of allergy and clinical immunology》1997,100(6):771-774
Background: Chronotherapy studies with inhaled corticosteroids have shown optimal therapeutic benefit when steroids are administered four times per day (QID) or once daily at 3 PM.Objective: This study evaluated whether more convenient once-daily dosage times (8 AM and 5:30 PM) produce improvement in asthma equivalent to QID.Methods: Efficacy outcome measures included FEV1, peak expiratory flow rates, bronchial responsiveness, use of β2-agonists, nocturnal awakenings, and responses to a quality of life questionnaire. Systemic effects were blood eosinophil count, cortisol level, 24-hour urinary cortisol, and evaluation for oral candidiasis and dysphonia.Results: Baseline measurements for all three treatment groups were similar. For morning peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.001) and the 5:30 PM group (p = 0.003), but not the 8 AM group (p = 0.75). For evening peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.005) and the 5:30 PM group (p = 0.01), but not for the 8 AM group (p = 0.47). There were significant improvements in all other outcome variables for each group except PC20. There was a significant improvement in PC20 only in the QID group. The systemic effects of the three regimens were comparable.Conclusion: Dosing of inhaled steroid at 5:30 PM had no increased systemic effects and produced efficacy similar to QID dosing. Dosing at 8 AM did not produce results consistently comparable to QID dosing. Optimal once-daily dosing of inhaled steroid is between 3 PM and 5:30 PM. 相似文献
104.
Mark J. Roth MD L.Jeffrey Medeiros MD Sudesh Kapur MD Leonard H. Wexler MD Sharon Mims BS Marc E. Horowitz MD Maria Tsokos MD 《Human pathology》1993,24(12)
We describe an infant girl, born with a pigmented giant nevus, who developed a malignant schwannoma in the retroperitoneum at 16 months of age. At birth the nevus covered over 50% of her body and histologically was a compound nevus with extension into the deep dermis surrounding dermal appendages. The malignant schwannoma was biphasic with areas composed of spindle and round cells. Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell phenotype, but neuroepithelial and melanocytic cells were identified as well. We believe that this constellation of findings represents a form of neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409–429, 1974), is a disease that results from aberrations in the migration, growth, or cytodifferentiation of neural crest tissues. These diseases may be simple (a singular pathologic process, usually localized) or complex (multiple neuroectodermal lesions). We report this case because the occurrence of retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a pigmented giant nevus is unique, and may represent a previously undescribed form of a complex neurocristopathy. 相似文献
105.
Charles V. Klucka DO Dennis R. Ownby MD Jack Green BS Edward Zoratti MD 《The Journal of allergy and clinical immunology》1995,95(6)
Background: No published studies have compared the effectiveness of several treatments proposed to reduce cat allergenicity. Cat washing studies demonstrating efficacy involved very small sample sizes or infrequent washings. Allerpet-C (Allerpet, Inc., New York, N.Y.), a widely advertised topical spray, and acepromazine, a tranquilizer advocated as efficacious in subsedating doses, have never been scientifically studied. Objective: We compared the effects of cat washing, Allerpet-C spray, and acepromazine with that of no treatment on the shedding of the primary cat allergen, Felis domesticus I by cats. Methods: In a blinded, comparative, controlled study, we measured the amounts of Fel d I shed during an 8-week treatment period with a sample of 24 female mongrel cats randomly assigned to four groups; one group received weekly distilled water washings, one received weekly Allerpet-C spray applications, one received daily oral acepromazine, and one had no treatment (control). Thirty-minute, twice-weekly air samples were collected from each cat with a laminated plastic–acrylic chamber and air sampler. Results: One-sample, two-sided t tests comparing baseline to final-week measurements revealed no significant change in Fel d I within each group (mean change ±SD: washing; 487.6 ± 1896.4 mU per 30 minutes, p = 0.63; Allerpet-C spray, 429.2 ± 871.6 mU per 30 minutes, p = 0.46 acepromazine; −620.6 ± 1031.2, p = 0.52 per 30 minutes). Furthermore, analysis of covariance revealed no significant change in Fel d I levels between groups (p = 0.72). Conclusions: Our data do not show significant reductions in Fel d I shedding as a result of any of these treatments. Therefore we cannot recommend them to patients allergic to cats. (J ALLERGY CLIN IMMUNOL 1995;95:1164-71.) 相似文献
106.
Atsushi Ohashi PhD Hirohisa Kotera BS Hideo Hori BS Makoto Hibiya PhD Koji Watanabe MD PhD Kazutaka Murakami MD PhD Midori Hasegawa MD PhD Makoto Tomita MD PhD Yoshinobu Hiki MD PhD Satoshi Sugiyama MD PhD 《Journal of artificial organs》2005,8(4):252-256
Polyvinyl chloride (PVC) tubing is an indispensable medical material for extracorporeal circulation therapy. However, di(2-ethylhexyl)phthalate
(DEHP), a suspected endocrine disruptor, can be eluted from PVC, suggesting that an alternative material that does not contain
DEHP is needed for clinical applications. First, we evaluated the endocrine disrupting risks of the plasticizers contained
in PVC tubes by investigating their binding affinities for the human estrogen receptor alpha (ERα). Our results revealed that,
while DEHP has some binding affinity for ERα, neither epoxidized soybean oil nor tris(2-ethylhexyl)trimellitate (an alternative
to DEHP) has any affinity for ERα. Second, we evaluated the endocrine disrupting risks of a tube made of newly developed plasticizer-free
(PF) materials. We confirmed the presence of DEHP and detected several unidentified substances in plasma stored within the
PVC tube. This plasma's competitive binding affinity for ERα was significantly higher than that of control plasma (P < 0.01). In contrast, the profile of plasma stored in the PF tube was similar to that of the control, both in terms of high-performance
liquid chromatography chromatograms and competitive binding capacity for ERα, suggesting that the PF tube is biocompatible
and is useful for reducing the elution of substances capable of binding to ERα.
Presented in part at the 42nd Congress of the Japanese Society for Artificial Organs, October 5–7, 2004, Tokyo, Japan 相似文献
107.
Jay E. Slater MD Elizabeth J. Paupore BS Michael R. Elwell DVM PhD Wava Truscott PhD 《The Journal of allergy and clinical immunology》1998,102(6):977-983
Background: LPS is a common contaminant in the health care environment and in latex examination gloves. Objective: We sought to investigate the role of LPS in enhancing the immune responses of mice to inhaled latex allergen. Methods: As our model allergen, we used a fusion protein containing the potent latex allergen Hev b 5. BALB/c mice were lightly anesthetized and given repeated intranasal doses of saline, LPS, and/or Hev b 5. The doses were given in 2 courses separated by a 6-week period, with the first course consisting of 6 doses and the second consisting of 3 doses. Results: After the first set of immunizations, mice given Hev b 5 alone had no detectable IgG1 or IgE responses to Hev b 5, whereas mice given the antigen along with LPS had significant responses (IgG1, 0.73 U ± 0.05; IgE, 0.88 U ± 0.2). No enhancement of specific IgG2a was observed. A stimulatory effect of LPS on all 3 immunoglobulin types was apparent after the second course. Lymphocytes from mice immunized with LPS and Hev b 5 had increased proliferation to Hev b 5 and its fusion partner. Conclusions: LPS may be an important immunoadjuvant for the development of allergic reactions to latex protein allergens. (J Allergy Clin Immunol 199;102:977-83.) 相似文献
108.
Donald Y. M. Leung MD PhD Donna M. Ambrosino MD Robert D. Arbeit MD Julie L. Newton BS Raif S. Geha MD 《The Journal of allergy and clinical immunology》1988,81(6):1082-1087
Patients with the hyper-IgE (HIE) syndrome have recurrent bacterial infections with Staphylococcus aureus and other polysaccharide encapsulated organisms. To determine whether an impairment of the antibody response to polysaccharide antigens contributes to infections in this syndrome, we measured serum antibody to the teichoic acid of S. aureus and to the capsular polysaccharide of Haemophilus influenzae type b. Compared to control subjects who had no history of S. aureus infections (N = 14), sera from patients with HIE (N = 9) lacked the expected elevation of serum antibody to teichoic acid (p greater than 0.05) and had significantly lower levels of this antibody than sera from 14 patients with atopic dermatitis, complicated by recurrent cutaneous S. aureus infections (p less than 0.01). After immunization with the capsular polysaccharide of Haemophilus influenzae type of vaccine, the antibody response of patients with HIE was significantly impaired compared to that of age-matched control subjects (p = 0.01). Although patients with HIE syndrome had normal total IgG levels, most patients with HIE but not patients with atopic dermatitis had IgG2 subclass deficiency. Defective antibody responses in patients with HIE were not restricted to polysaccharide antigens because the serum levels of antitetanus toxoid antibody in these patients were significantly lower than that of control subjects (p less than 0.001). Impaired antigen-specific antibody responses in patients with HIE syndrome may contribute to their increased susceptibility to infection. 相似文献
109.
Johanna L. Schmidt MPH MGC CGC Amy Pizzino MS CGC Jessica Nicholl MS CGC Allison Foley MMSc CGC Yue Wang PhD FACMG Jill A. Rosenfeld MS CGC Lindsey Mighion MS CGC Lora Bean PhD Cristina da Silva MS Megan T. Cho MS CGC Rebecca Truty PhD John Garcia PhD Virginia Speare PhD Kirsten Blanco BS Zoe Powis MS CGC Grace M. Hobson PhD Susan Kirwin BS Bryan Krock PhD FACMG Hane Lee PhD Joshua L. Deignan PhD Maggie A. Westemeyer MS CGC Ryan L. Subaran PhD Isabelle Thiffault PhD FABMGG Ellen A. Tsai PhD Terry Fang PhD Guy Helman BS Adeline Vanderver MD 《American journal of medical genetics. Part A》2020,182(8):1906-1912
Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening. 相似文献
110.
Chaturvedi V Chu MD S Carrol BS M Brenner BS JW Nickoloff BJ 《Archives of pathology & laboratory medicine》2002,126(4):420-424
OBJECTIVE: It has been suggested that keratinocyte (KC) stem cells reside at the epicenter of a clonal population of cells. To estimate the territory or surface area covered by a single stem-cell-derived KC population in human skin, clonal skin maps were created from 3 healthy adult women and from normal skin of a psoriatic patient. DESIGN: Two hundred fifty-eight punch biopsy samples of various sizes (ranging from 2 to 8 mm in diameter) were analyzed for clonality employing X chromosome inactivation patterns at the human androgen receptor gene (HUMARA) locus. DNA was isolated and clonality established by significant decrease of either maternal or paternal X chromosome band patterns following restriction enzyme digestion, polymerase chain reaction amplification, and gel electrophoresis. RESULTS: Fifty-three (41%) of 128 two-mm biopsies were clonal, whereas only 6 (14%) of 43 three-mm, 5 (14%) of 36 four-mm, and 3 (8%) of 35 five-mm biopsies revealed a clonal population of KCs. By contrast, in 5 different biopsies from a psoriatic patient, including 4- or 5-mm sizes, all but 1 were clonal; even an 8-mm biopsy contained a clonal population of KCs. Mantel-Haenszel chi(2) analysis revealed a P value of.001, reflecting a strong trend in probability for presence of a single clone of KCs as related to size of the biopsy sample. By sequentially analyzing 30 contiguous 2-mm biopsy samples within a given strip of skin, 10 clonal domain changes, as reflected in maternal versus paternal switches, were observed. CONCLUSIONS: These results provide direct evidence of a clonal population of KCs in normal and psoriatic lesion-free skin, and indicate that a clonal epidermal unit of KCs frequently can be detected in small biopsies (2 mm), but that in normal skin sampling, overlapping clones are apparently present in larger (ie, 4-5-mm) biopsies, producing nonclonal patterns. The clonal domain of progeny in normal skin has a rather limited territorial boundary (2 mm in diameter). However, in lesion-free skin from a psoriatic patient, there may be clonal expansion of KCs due to perturbation in epidermopoiesis and/or stem cell distribution. 相似文献