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81.
The bias favoring deletion over inversion in DH-JH rearrangement has been
known for years, but the underlying mechanism has yet to be fully defined.
It has been suggested that the ratio of deletion/inversion is determined by
the combined effect of two factors: (i) the relative strengths of 5' and 3'
recombination signal sequences (RSS) of a DH segment, and (ii) the
efficiency with which the deletional product (one joint) forms relative to
the inversional product (two joints). In this study, we analyzed for the
first time the effect of factor 1 alone on the biased 3' RSS utilization in
DH-JH joining by using deletional plasmids in an extrachromosomal substrate
V(D)J recombination assay. It was found that the 3' RSS and associated
coding end (12 bp) mediate recombination more efficiently than the 5'
RSS/coding end DH-JH plasmids. These results demonstrate that the effect of
the RSS/coding end alone can account, at least partially, for the
predominant deletion in DH-JH recombination. The potential effect of the
relative strength of RSS and associated coding end on the ordered
rearrangement of DH-JH followed by VH to DH-JH was also assessed. When
recombination frequencies of D-->J (3' DH to J3) were compared with
frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found
that V-->D joining was, if anything, more efficient than D-->J
joining. Therefore, if all three segments were accessible, RSS/coding end
effects would not contribute to the ordered rearrangement of the IgH locus.
相似文献
82.
JM Hopkin 《Current opinion in immunology》1997,9(6):788-792
Atopy — a T helper 2 cell driven hypersensitivity to innocuous antigens (allergens) which causes most cases of asthma — is of complex genetic and environmental origins. There is compelling epidemiological evidence for a rise in atopic disease in ‘westernised’ communities. The changing pattern of microbial exposure in early childhood is suggested to be the principal candidate mechanism for this rise. 相似文献
83.
84.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
85.
86.
Huang XH Loimaala A Nenonen A Mercuri M Vuori I Pasanen M Oja P Bond G Koivula T Hiltunen TP Nikkari T Lehtimäki T 《Journal of molecular medicine (Berlin, Germany)》1999,77(12):853-858
The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50-59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18 +/- 0.30, 1.22 +/- 0.24, and 1.08 +/- 0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis. 相似文献
87.
DL?MagerEmail author AD?Haffajee PM?Devlin CM?Norris MR?Posner JM?Goodson 《Journal of translational medicine》2005,3(1):27
Background
The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. 相似文献88.
Skin and anal mucosal carriage of Malassezia spp. yeasts was investigated in 21 healthy Devon Rex cats (DRC) and in 9 seborrhoeic DRC using swabs and contact plates. M. pachydermatis was isolated from 26 cats and lipid-dependent Malassezia spp. isolates were recovered from the claw fold of 5 healthy and 3 seborrhoeic DRC. The frequencies of isolation and population sizes of M. pachydermatis in the axillae, left groin and claw fold in seborrhoeic DRC significantly exceeded (P<0.05) those of healthy animals. The frequencies of isolation and population sizes of M. pachydermatis in the axillae and groin in both groups of DRC, and the frequencies of isolation and population sizes of M. pachydermatis in the claw fold of the seborrhoeic DRC, exceeded those of healthy Domestic short-haired cats. Using polymerase chain reaction--restriction enzyme analyses (PCR-REA) based on amplification of the large subunit rRNA gene, all eight lipid-dependent isolates had profiles that were indistinguishable from that of M. slooffiae CBS 7956. These data indicate that DRC are frequently colonized by M. pachydermatis and that the claw folds may also be colonized by M. slooffiae. The pathogenic significance of the high Malassezia spp. counts in the seborrhoeic DRC should now be determined. 相似文献
89.
Hormone replacement therapy can successfully treat menopausal symptoms. A postal questionnaire was used to investigate the knowledge of and attitudes to hormone replacement therapy of an age-stratified, computer-generated, representative sample of 1500 women living in the Grampian region of Scotland. A response rate of 78% was achieved. Comparisons were made between women of differing age, educational background and their current or past experience of hormone replacement therapy. The questionnaire also assessed their knowledge of osteoporosis, including the possible beneficial role of hormone replacement therapy. The results showed that women had a poor knowledge of the potential risks and benefits of oestrogen, lack of knowledge being greatest in the less educated and older women. The majority of women agreed with the view that because the menopause is brought on by diminished hormone levels, it should be viewed as a medical condition and treated as such, and also that a woman who experiences distressing menopausal symptoms should take hormone replacement therapy. Despite this, relatively few postmenopausal women were currently taking hormone replacement therapy (9%) or had taken the treatment in the past (7%), although many had experienced menopausal symptoms for over six months. The most common reason for postmenopausal women never having taken hormone replacement therapy was that they had never considered the treatment (70%) and had not discussed it with a doctor (79%).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
90.
Cramer LG Pitt SR Rehbein S Gogolewski RP Kunkle BN Langhoff WK Bond KG Maciel AE 《Parasitology research》2000,86(11):944-946
Six studies were conducted to evaluate the persistent efficacy of eprinomectin pour-on against experimental challenges with
infective nematode larvae in calves. In each study, calves were randomly assigned to one untreated group and up to four test
groups, which were treated with eprinomectin at 500 μg/kg body weight at weekly intervals before single bolus challenge. The
calves were necropsied approximately 4 weeks after challenge infection for nematode recovery. Eprinomectin pour-on provided
≥90% efficacy against challenge with Haemonchus placei, Trichostrongylus axei and T. colubriformis at 21 days after treatment and against Cooperia oncophora, C. punctata, C. surnabada, Dictyocaulus viviparus, Nematodirus helvetianus, Oesophagostomum radiatum and Ostertagia ostertagi at 28 days after treatment.
Received: 14 April 2000 / Accepted: 18 May 2000 相似文献