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排序方式: 共有1124条查询结果,搜索用时 15 毫秒
141.
Nan Zhong Krystyna E. Wisniewski Jaana Hartikainen Weina Ju Dorota N. Moroziewicz Lucille McLendon Susan Sklower Brooks W Ted Brown 《Clinical genetics》1998,54(3):234-238
Zhong N, Wisniewski KE, Hartikainen J, Ju W, Moroziewicz DN, McLendon L, Sklower Brooks S, Brown WT. Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis
Late infantile neuronal ceroid lipofuscinosis (LINCL) is one of the most common pediatric neuronal degenerative disorders. A candidate gene underlying this disease, designated CLN2, was recently cloned and the gene product was characterized as a lysosomal pepstatin-insensitive carboxypeptidase (LPIC). Four mutations were identified in CLN2 from three unrelated LINCL individuals. To investigate further the mutation frequency in LINCL, we screened 16 LINCL probands for these four mutations. The previously reported intronic mutation, T523–1 G°C, was found in 56% (9/16) of the cases, of which two were homozygous and accounted for 34% (11/32) of LINCL chromosomes. The previously reported nonsense mutation, 636 C→T leading to R208stop, was found in 31% (5/16) of the cases, including one ho-mozygote and accounted for 19% (6/32) of LINCL chromosomes. Two previously described missense mutations, 1107 T°C and 1108 G→A, were not detected in any of these 16 probands. In total, the two observed mutations, T523–1 G°C and 636 C→T, accounted for 53% (17/32) of LINCL alleles. Thus, one or both mutations were seen in 11 (69%) cases and no mutation has yet been identified in five. Our finding that these two mutations are common in LINCL cases adds further evidence in support of the idea that dysfunction of LPIC underlies LINCL. Positive molecular testing can now complement clinical diagnosis of LPIC and will allow for pre-natal diagnosis for subsequent pregnancies. 相似文献
Late infantile neuronal ceroid lipofuscinosis (LINCL) is one of the most common pediatric neuronal degenerative disorders. A candidate gene underlying this disease, designated CLN2, was recently cloned and the gene product was characterized as a lysosomal pepstatin-insensitive carboxypeptidase (LPIC). Four mutations were identified in CLN2 from three unrelated LINCL individuals. To investigate further the mutation frequency in LINCL, we screened 16 LINCL probands for these four mutations. The previously reported intronic mutation, T523–1 G°C, was found in 56% (9/16) of the cases, of which two were homozygous and accounted for 34% (11/32) of LINCL chromosomes. The previously reported nonsense mutation, 636 C→T leading to R208stop, was found in 31% (5/16) of the cases, including one ho-mozygote and accounted for 19% (6/32) of LINCL chromosomes. Two previously described missense mutations, 1107 T°C and 1108 G→A, were not detected in any of these 16 probands. In total, the two observed mutations, T523–1 G°C and 636 C→T, accounted for 53% (17/32) of LINCL alleles. Thus, one or both mutations were seen in 11 (69%) cases and no mutation has yet been identified in five. Our finding that these two mutations are common in LINCL cases adds further evidence in support of the idea that dysfunction of LPIC underlies LINCL. Positive molecular testing can now complement clinical diagnosis of LPIC and will allow for pre-natal diagnosis for subsequent pregnancies. 相似文献
142.
The mechanism of action of the topoisomerase II inhibitor etoposide(VP-16) was investigated in male mouse meiosis using the spermatidmicronucleus (MN) test and two molecular cytogenetic approaches:(i) fluorescence in situ hybridization (FISH) with a mouse centromerespecific minor satellite DNA probe; and (ii) immunolabellingof kinetochore proteins with CREST autoimmune serum. VP-16 causedsignificant increases in the frequencies of MN at all meioticstages studied. VP-16 induced MN showed significantly elevatedfrequencies of centromeric hybridization signals compared tothe controls. Similarly, after CREST immunostaining the majorityof MN induced by the drug showed kinetochore signals when meioticS phase and diplotene-diakinesis were treated. This would suggestthat most induced MN were due to lagging of whole chromosomes.However, more than 80% of the small MN observed were signal-positiveand a large pool of minute MN almost exclusively (92%) containeda kinetochore or centromere-DNA signal. This indicates thatVP-16 causes chromosome fragmentation at centromeres. In addition,arrested first division (MI) anaphase figures with stretchedbivalent(s) at the spindle equator were observed when diplotene-diakinesisand MI were targeted. Moreover, many small and medium size MNhad two centromere or kinetochore signals at opposite sides,suggesting that inhibition of topo II at MI causes lagging ofwhole bivalents. Together, these results indicate that VP-16acts by several genotoxic mechanisms at male meiosis: (i) fragmentationof centromeres possibly as a result of inhibition of the DNAstrand religation reaction in a topoisomerase II mediated decatenationprocess of sister centromeres; and (ii) the induction of aneuploidyas a result of failures in separation of homologous chromosomearms possibly due to disturbances of chiasma resolution anddecatenation processes during MI. Our results indirectly suggestthat topoisomerase II plays an important role in male meiosisand its activity is needed at the metaphase-anaphase transitionof both meiotic divisions for proper chromosome disjunction.
1To whom correspondence should be addressed 相似文献
143.
T. Salonen Antti Haapalinna Esa Heinonen Jaana Suhonen Antti Hervonen 《Acta neuropathologica》1996,91(5):466-474
Selegiline is a selective and irreversible monoamine B inhibitor with the capacity to increase the level of several antioxidative
enzymes in rat brain. It can protect adrenergic neurons against injury induced by neurotoxins such as MPTP, DSP-4 and AF64A
in animal studies. In addition, the protective action is not limited to catecholaminergic cells, as selegiline can also minimize
the loss of developing motoneurons after axotomy. The aim of this study was to determine whether selegiline can protect peripheral
catecholaminergic neurons against the neurotoxic effect of 6-OHDA. This kind of protective effect against 6-OHDA neurotoxicity
has not been reported before. Wistar albino male rats aged 4 or 24 months were treated with selegiline or saline solution
1 h before 6-OHDA injection. At 2 weeks after the 6-OHDA injection, the superior cervical ganglia (SCG) and submandibular
glands (SMG) were studied using catecholamine histofluorescence and immunohistochemistry for tyrosine hydroxylase (TH). The
number of TH-positive cells in the SCG and the length and number of adrenergic nerve fibers in the SMG were quantified. Our
findings showed that 6-OHDA caused a reduction of TH immunoreactivity and catecholamine histofluorescence in neuronal somata,
as well as a decrease in the number and length of adrenergic nerve fibers in the submandibular gland. Selegiline pretreatment
protected SCG neurons and their postganglionic nerve fibers in SMG against these changes in a dose-dependent manner. The mechanism
through which selegiline exerts its neuroprotective effect is as yet unknown.
Received: 5 September 1995 / Revised, accepted: 13 November 1995 相似文献
144.
Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra 总被引:6,自引:0,他引:6
Juha O. Rinne Jaana Rummukainen Mlic Leo Paljrvi Urpo K. Rinne 《Annals of neurology》1989,26(1):47-50
Regional neuronal loss in the substantia nigra was studied in relation to extrapyramidal symptoms and dementia in 12 patients with idiopathic Parkinson's disease (PD) and in 18 control subjects. Four areas of the right substantia nigra were investigated at the level of the superior colliculus and caudal red nucleus. In Parkinson's disease, the percentages of neurons, from the medial to the lateral part of the substantia nigra, were reduced to 49%, 31%, 41%, and 25% of the control values. The number of neurons in the lateral part showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor was less noticeable in patients with few neurons. The degree of dementia of the patients had a significant correlation only with neuronal loss in the medial part of the substantia nigra, suggesting, in view of the topographical organization of the neurons in the substantia nigra, that intact projections to the caudate nucleus and limbic and cortical areas are a prerequisite for normal cognitive functioning and that their dysfunction leads to clinical dementia. 相似文献
145.
We have studied the effects of vinblastine sulfate (VBL) and colchicine (COL) on male rat in vivo and in vitro meiosis. A novel methodology based on isolating a segment of seminiferous tubules containing meiotically dividing spermatocytes was applied. During meiotic divisions at stage XIV of rat spermatogenesis, both chemicals induced only low frequencies of micronu-clei (MN), 0.8–3.2 MN/1,000 spermatids. Fluorescence in situ hybridization experiments in mice with the mouse centromere-specific y-sat-ellite DNA probe showed that 50.7% of VBL-induced MN and 56.6% of COL-induced MN were centromere positive, indicating that the MN induced by both chemicals contained detached chromosomes. The inhibition of cell proliferation was determined by counting the number of cells arrested at metaphase during the first meiotic (MI) or the second meiotic (MII) division. VBL was found to be a potent inducer of cell death while COL was not. The direct effects of VBL and COL on the meiotic spindles were evaluated using immunohistochemistry with anti-a-tubulin and confocal microscopy. In the control animals a significant difference was observed between the mean length of metaphase spindles of MI and MII Both were dramatically decreased 6 hr after treatment with 2.0 mg/kg of VBL and 0.8 mg/kg of COL, respectively. At 18 hr after COL injection the spindles had about the same length as in the controls. However, the VBL-induced shortening was even more evident at 18 hr for both Ml and Mll. The possible reasons for observed differences between the two chemicals and between meiosis and mitosis are discussed. © 1995 Wiley-Liss, Inc. 相似文献
146.
147.
Puntila J Hakala T Salminen J Pihkala J 《Interactive Cardiovascular and Thoracic Surgery》2006,5(5):662-663
Less than 10% of cardiac myxomas are familial. These familial cases are related to Carney complex, a multiple neoplasia and lentiginosis syndrome. Mutations in the PRKAR1alpha gene are the cause of Carney complex in most patients. We report a boy, who had PRKAR1alpha gene mutation, and atrial myxoma that was diagnosed in a routine echocardiographic study at the age of four years. Surgical excision of myxoma was performed. This case demonstrates the benefit of screening genetically the kindreds of patients with familial myxomas, and the importance of close follow-up of individuals affected with this mutation irrespective of age. 相似文献
148.
H Isom?ki J Martio K Kaarela A Kajander K Koota K Lehtinen R Luukkainen T Martio M Nissil? P Nuotio 《British journal of rheumatology》1984,23(1):61-65
The analgesic effect of 10 anti-inflammatory drugs was compared using a single-blind method in 90 patients with rheumatoid arthritis. Each patient received two different drugs, for three days each and each drug was evaluated in 18 patients. After the trial, the patients considered which of the drugs they preferred. The greatest relief from pain was achieved by diclofenac, indomethacin, naproxen and tolfenamic acid, each of these being preferred by the majority of patients and being significantly (p less than 0.01) better than the least effective drugs ketoprofen and proquazone. Acetylsalicylic acid, azapropazone, carprofen and ibuprofen were considered intermediate in efficacy. 相似文献
149.
BACKGROUND: Although human papillomaviruses (HPVs) are associated with a number of proliferative epithelial lesions including squamous cell malignancies, they can also be detected in the normal oral mucosa in 10% to 20% of the adult population. However, the point of entry and the site of replication of HPV in the oral cavity are not known. Since the gingival pocket is the only site in the oral mucosa where basal cells, known to be targets of HPV at other mucosal sites, are normally exposed to the environment, we hypothesized that this could be the site of latent HPV. METHODS: Gingival biopsies taken from 38 individuals with clinically diagnosed periodontal disease were examined. The presence of HPV DNA was studied by using nested PCR (polymerase chain reaction with MY09/MY11 and GP05+/GP06+ primers targeting the L1 region of HPV), followed by subsequent hybridization with a cocktail of 12 high-risk HPV oligoprobes and in situ hybridization (ISH) with probes for HPV screening and the HPV subtype 16. RESULTS: In the present study, high-risk HPV types were detected in 26% (8/31) of the gingival biopsies with PCR. By using in situ hybridization, the viral DNA was localized to the coronal part of the junctional epithelium in the gingival pocket. CONCLUSIONS: The results suggest that the periodontal pocket might serve as a reservoir of HPVs in oral mucosa. While having important implications in understanding the HPV transmission, this observation does not rule out the possibility that HPV may be involved in the initiation of periodontal disease. 相似文献
150.
Selja?Koskensalo Jaana?Hagstr?m Nina?Linder Mikael?Lundin Timo?Sorsa Johanna?Louhimo Caj?HaglundEmail author 《BMC clinical pathology》2012,12(1):24